review article carbon nanotubes: an emerging drug carrier ...the laser ablation and the chemical...

Review ArticleCarbon Nanotubes An Emerging Drug Carrier forTargeting Cancer Cells

Vaibhav Rastogi1 Pragya Yadav1 Shiv Sankar Bhattacharya1 Arun Kumar Mishra1

Navneet Verma1 Anurag Verma1 and Jayanta Kumar Pandit2

1 School of Pharmaceutical Sciences IFTM University Moradabad Uttar Pradesh 244001 India2Department of Pharmaceutics Institute of Technology Banaras Hindu University Varanasi Uttar Pradesh 221005 India

Correspondence should be addressed to Vaibhav Rastogi vaibasagmailcom

Received 23 October 2013 Revised 26 January 2014 Accepted 12 March 2014 Published 24 April 2014

Academic Editor Hans E Junginger

Copyright copy 2014 Vaibhav Rastogi et alThis is an open access article distributed under theCreative CommonsAttribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

During recent years carbon nanotubes (CNTs) have been attracted bymany researchers as a drug delivery carrier CNTs are the thirdallotropic form of carbon-fullerenes which were rolled into cylindrical tubes To be integrated into the biological systems CNTs canbe chemically modified or functionalised with therapeutically activemolecules by forming stable covalent bonds or supramolecularassemblies based on noncovalent interactions Owing to their high carrying capacity biocompatibility and specificity to cellsvarious cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters cell viability cytotoxicty anddrug delivery in tumor cellsThis review attempts to highlight all aspects of CNTs which render them as an effective anticancer drugcarrier and imaging agent Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomoleculesand anticancer drugs has been covered in this review

1 Introduction

After the discovery of the third allotropic form of carbonfullerene in 1991 Sumio Iijima identified a new structuralform of this allotrope the cylindrical fullerene and namedthem as carbon nanotubes (CNTs) [1] CNTs are graphenesheets rolled into a seamless cylinder that can be openended or capped having a high aspect ratio with diametersas small as 1nm and a length of several micrometers [2]Depending on the number of sheets rolled into concentriccylinders there are two broad categories of CNTs namelysingle-walled carbon nanotubes (SWCNTs) and multiwalledcarbon nanotubes (MWCNTs) (Figure 1) SWCNTs are madeup of single graphene layer wrapped into a hexagonal close-packed cylindrical structure whose diameter varies from04 to 30 nm and length ranges from 20 to 1000 nm and areheld together by Vander Waals forces which makes themeasily twistable and more pliable [3] SWCNTs are producedby the electric arc [4] laser ablation [5] chemical vapordeposition (CVD) [6] and gas-phase catalytic processes(HiPco or high-pressure CO conversion) [7]

MWCNTs consist of several coaxial cylinders each madeof a single graphene sheet surrounding a hollow core Theouter diameter of MWCNTs ranges from 2 to 100 nm whilethe inner diameter is in the range of 1ndash3 nm and their lengthis 1 to several 120583m [8] Electric arc [9] and chemical vapordeposition (CVD) [10 11] are the main techniques for theirproduction Owing to the sp2 hybridization in MWCNTs adelocalized electron cloud along the wall is generated whichis responsible for the 120587-120587 interactions between adjacentcylindrical layers in MWCNTs resulting in a less flexible andmore structural defects [12]

With more than 10 million new cases every year canceris one of the most devastating diseases Though the currenttreatments of cancer by surgery radiation and chemother-apy are successful in several cases however these curativemethods are likely to kill healthy cells and cause toxicityto the patient [13] Many patients who succumb to deathdue to cancer do not die as a result of the primary tumorbut because of the systematic effects of metastases on theother regions away from the original site One of the aims ofcancer therapy is to prevent the metastatic process as early as

Hindawi Publishing CorporationJournal of Drug DeliveryVolume 2014 Article ID 670815 23 pageshttpdxdoiorg1011552014670815

2 Journal of Drug Delivery

04ndash30nm

200

ndash10000

nm

(a)

10ndash30nm

20ndash1000 nm

(b)

Figure 1 Carbon nanotube (a) single walled carbon nanotube and (b) multiwalled carbon nanotube

possibleTherefore significant amounts of research have beencarried out to overcome these problems The main problemincurred with various chemotherapies for treating cancer islack of selectivity of the anticancer drug towards cancerouscells This nonspecificity of the drug limits the therapeuticdosewithin cancer cells while providing excessive toxicities tonormal cells tissues and organs and thereby causing severaladverse effects Besides precise tumor targeting and toxicityconcerns drug resistance remains a major obstacle for thetreatment of advanced cancerous tumor [14ndash16] ldquoCancernanotechnologyrdquo is the novel emerging field which usednanocarriers like liposome polymeric nanoparticles den-drimers quantum dots polymersomes carbon nanotubesand so forth for delivering drugs to the target site and thusholds tremendous potential to overcome several problemsassociated with the conventional therapies [17 18] Apartfrom the several advantages of these nanocarriers some ofthem pose challenges of their own For instance liposomeshave been used as a potential carrier with unique advantagesincluding protecting drugs from degradation reduction intoxicity or side effects but the applications of liposomes werefound to be limited due to the inherent problems such aslow encapsulation efficiency poor solubility of many drugsin the lipidsurfactant solution and rapid leakage of watersoluble drug in the presence of blood components as wellas unpredictable storage stability [19] Since precise tumortargeting with reduction in toxicity is the chief objective incancer therapy some nanocarriers like immunoliposomes(a class of liposomes) exhibit their inability to activelytarget the specific cells because the ligands conjugatedwith liposomes may increase the liposome size and reduceextravasation which may tend to be rapidly cleared by thecells of reticuloendothelial system (RES) [20] Similarlytargeted nanoparticles (NPs) also facedmany challenges Onechallenge faced by targeting NPs is that NPs might changethe stability solubility and pharmacokinetic properties ofthe carried drugs while another challenge is associated withthe shelf life aggregation leakage and toxicity of materials

used to make NPs for example poly (lactic-co-glycolicacid) (PLGA) a polymer of choice nowadays among theresearchers to fabricate NPs because of their low toxicity andhigh targeting efficiency but they degrade quickly and donot circulate in tissues long enough for sustained druggenedelivery which limits their usability in long term cancertherapy On the other hand CNTs can persist in the bodyfor weeks months or even years thus limiting their use forrepeated treatments [15 21] If we talk about dendrimers theyare synthetic branched macromolecules that form a treelikestructure whose synthesis represents a relatively new field inpolymer chemistryThough promising dendrimers are moreexpensive than other nanocarriers like CNTs and requiremany repetitive steps for synthesis posing a challenge forlarge-scale production [22] In the recent years of researchreported data clearly reveals that CNTs have an enormouspotential and possess high entrapment efficiency to carrythe therapeutic molecule as earliest to the site of cancer cellwithout activating the immune system and damage to otherviable cells although toxicity issues related to CNTs are underresearch This review highlights the insights of the CNTs andtheir potency in delivering the anticancer drugs to combatvarious metastatic cancer cells specifically

2 Production of CNTs

The production of CNTs complies with the transformation ofa carbon source into nanotubes usually at high temperatureand low pressure wherein the synthesis conditions influencethe characteristics of the final product Since prepared CNTsare usually associated with carbonaceous or metallic impu-rities therefore purification is an essential step to be con-sidered [23] Methods of CNTs purification include chemicalmethods particularly oxidation (gas phase [24] liquid phase[25]) physical methods (filtration [26] centrifugation [27]and high temperature annealing [28] etc) and multisteppurification [29]

Journal of Drug Delivery 3

Powersource

(+)

C deposit

Pump Gas

Linear motionactuator

(minus)Anode Cathode

(a)

CnHn

Substrate

gasCarrierOutlet

coilsHeatingchamber

Reaction

collectorcooledWater

depositsCarbon

(b)

chamberReaction


depositsCarbon

Nd-yaglaser

Graphitetarget

Furnace

(c)

Figure 2 Schematic representation ofmethods used for carbonnanotube synthesis (a)Arc dischargemethod (b) chemical vapour depositionmethod (c) laser ablation method

Presently there are threemain approaches for the synthe-sis of CNTs (Figures 2 and 3) including electric arc dischargethe laser ablation and the chemical vapor deposition (CVD)

21 Arc Discharge Method This method is the oldest methodused by Iijima in 1991 when CNTs were first identified [1]Figures 2(a) and 3(a) showed the synthesis of CNTs by arcdischarge method In this method an arc is generated whena DC current of 200A to 20V is applied across two carbonelectrodes which are placed in a vacuum chamber that istypically filled with inert gas (Helium argon) at low pressure(sim50sim700mbar) The positive electrode is gradually broughtcloser to the negative one to strike the electric arc Theelectrodes become red hot and such an extreme conditionturns the gas into plasma a fluid of negatively and positivelycharged particles generating a temperature high enough tovaporize materials Once the arc stabilizes the electrodesare kept about a millimetre apart while the CNT depositson the negative electrode [30 31] The two most importantparameters to be taken care of in this method are (1) thecontrol of arcing current and (2) the optimal selection of inertgas pressure in the chamber

Ebbesen and Ajayan [9] for the first time reportedsynthesis of CNTs on a large scale and optimized the yieldof nanotubes by varying conditions such as type of inert gaspressure the nature of current (AC or DC) the voltage and

the relative rod size They showed the optimal yield of CNTsat 500 torr pressure In another study Ohkohchi et al studiedthe growth promoting effect of scandium on nanotubes byusing a carbon composite rod containing scandium oxide forthe synthesis of CNTs by arc discharge evaporation [32] Leeet al and Antisari et al reported high yield of MWCNTs byelectric arc discharge in liquid environments particularly inliquid nitrogen and deionised water [33 34] AlternativelyWang et al used sodium chloride solution as a liquidmediumbecause of its significant cooling ability and excellentelectrical conductivity than deionised water and concludedsuccessful synthesis of MWCNTs with the formation of asingle sheet of SWCNT [35] Anazawa et al demonstratedthe introduction of magnetic field in arc discharge synthesisto obtain high-puritydefect-free (purity gt 95) MWCNTs[36] Ando et al modified this method by a newly developedDC arc plasma jet method for the evaporation of metaldoped carbon anode They showed a high production rate(124 gmin) as compared to the conventional method [37]Cheng et al devised a hydrogen arc discharge method for theproduction of SWCNTs with high hydrogen capacity usinggraphite powder catalyst metal and a growth promoter in anatmosphere containing hydrogen [38]

The diameter and the linearity of the SWCNTs can becontrolled by the modification in the synthesis procedure Ina study Farhat et al altered the inert gas nature by increasing


Electric discharge fromelectrode to other

Coverts non-conductivegas to conductive gas

Carbon vaporizes fromcarbon substrate

Vaporized carbonreassemble to form

CNTs on the cathode

Gaseousenvironment

(a)

Decomposition of one ormore volatile carbonprecursors at high

temperature

Dissociation of hydrocarbon molecules

Precipitation of carbonfrom the saturated metal

particles leads to the formation of CNTs

(b)

Intense pulse of laserlight

Directed on

Carbon substrate andon small amount oftransition metals in a stream of Helium gas

Evaporated carbon deposited and

assembles to form CNTs

(c)

Figure 3 Mechanism of carbon nanotube synthesis (a) Arc discharge method (b) chemical vapor deposition method and (c) laser ablationmethod

the argon fraction in the inert gas mixture which resulted inthe decrease in nanotube diameter [39]

Further Kajiura et al also synthesized SWCNTs withnarrow diameter distributions using a DC arc dischargemethod with bimetallic combination (Yttrium-Nickel alloy)as a catalyst and Selenium as parameter [40] They showedthat SWCNTs obtained by thismethod can be readily purifiedup togt99with traditional purification as comparedwith theabove study by Farhat et al

Among several methods for preparing CNTs arc dis-charge is the most practical and inexpensive approach forscientific purposes because the method yields highly graphi-tized tubes due to high process temperatureHowever despiteof the above fact this method produces many byproductsbesidesCNTsAs a result the process requireswell-controlledpurification steps to maintain the quality of nanotubes andeliminate species such as amorphous carbon and metallicnanoparticles [41] Furthermore due to the relatively littlecontrol over the alignment (ie chirality) of the producednanotubes the characterization becomes complex

22 Chemical Vapour Deposition (CVD) While the arcdischarge method is capable of producing large quantitiesof unpurified nanotubes significant effort is being directedtowards production processes that offer more controllableroutes to the nanotube synthesis One of the such processis chemical vapour deposition (CVD) that seems to offerthe best chance to obtain a controllable process for theselective production of nanotubes with predefined properties[42] Apart from materials scale-up controlled synthesis ofaligned and ordered CNTs can be achieved by using CVD[43] The microstructure of the CNT tips synthesized bythe CVD technique exhibits well-formed caps compared toother techniquesTherefore CVD is the preferred method forproduction of CNTs over other methodsThe brief schematicrepresentation of this method is given in Figures 2(b) and3(b) In this method a mixture of hydrocarbon gas (ethylene

methane or acetylene) and a process gas (ammonia nitrogenand hydrogen) is made to react in a reaction chamber onheated metal substrate at a temperature of around 700∘Cndash900∘C at atmospheric pressures Residual gas diffuses awaywhereas free carbon atoms dissolve into the nanoparticlesand then segregate to the catalyst surface to form nanotubes[44]The key parameters include the nature of hydrocarbonscatalysts and the growth temperature Depending on thereaction conditions and catalyst preparations this methodmay be applied to obtain either SWCNTs or MWCNTs [45]

There are two possible mechanisms for the catalystassisted nanotube growth namely tip growth [46] and rootgrowth mechanism [47] Balbuena et al demonstrated therole of catalyst in the growth of SWCNTs by using modelCo-Mo catalyst and also studied the role of catalystsubstrateinteractions [48] They found that a strong clustersubstrateinteraction increases the cluster melting point modifying theinitial stages of carbon dissolution and precipitation on thecluster surface

In a study Hoffmann et al reported the critical effectsof NH

3or H2on Fe thin film catalyst restructuring which

enabled the surface bound growth of SWCNTs at temperatureas low as 350∘CbyCVD [49]They observed narrow diameterof the SWCNTs formed at low temperature Various effortshave been taken to modify this technique One such exampleis reported by Chen et al and Choi et al They showed thatby taking advantage of low temperature with the additionof microwave energy that is microwave plasma-enhancedCVD (PECVD) an increase was seen in the yield of verticallyaligned MWCNTs being successfully synthesized [50 51]In another study Huisken et al replaced the global heatsource for the furnace with a localized spot heated by alaser and thus studied the suitability of laser assisted CVD(LCVD) for the formation and growth of nanotubes In thisstudy they utilized medium power continuous wave CO

2

laser to irradiate a sensitized mixture of Fe(CO)5vapour

and acetylene to heat the silicon substrate simultaneously on


which CNTs were grown [52] Similarly Lackey et al alsodemonstrated the use of LCVD for the synthesis of CNTs[53] A novel continuous process registered by Khodadadiet al involves catalytic chemical vapour deposition (CCVD)ofmethane on iron floating catalyst in situ deposited onMgOin fluidized bed reactor for the production of CNTs [54]

A major drawback associated with the CVD technique isthat there are high defect densities in the MWNT structuresgrown by this process due to the lack of sufficient thermalenergy for annealing CNTs because of relatively low growthtemperature [55]

23 Laser Ablation Method This method was developedby Smalley et al in which direct laser beam was focusedon transition-metalgraphite composite rods to produceSWCNTs [56] In the laser ablation process a pulsed laseris made to strike at a graphite target in a high temperaturereactor (furnace) in the presence of inert gas such as heliumwhich vaporizes the graphite target and forms a laser plumeThe laser plume contains vaporized carbon and metallicnanoparticles that lead to the reassembling of carbon inthe form of carbon nanotubes The nanotubes develop onthe cooler surfaces of the reactor as the vaporized carboncondenses Nanotubes produced by laser ablation have higherpurity (up to about 90 pure) and their structure is bettergraphitized than those produced by the arc dischargemethodThe high cost of laser and small carbon deposit are the majorlimitations of this method In addition to this the methodmainly favors the growth of SWCNTs and special reactionconditions are required to generate MWCNTs [57]

Several researchers reported different modifications ofthe laser ablation method to improve the geometry andyield of SWCNTs (Figures 2(c) and 3(c)) In a study Maseret al used continuous wave 250W CO

2laser operating

at 106 120583m wavelength to evaporate graphitebimetal targetsand produced high densities bundles of SWCNTs [58] whileYudasaka et al showed an improved yield of SWCNTs bypulsed laser over a continuous one [59] Zhang et al studiedthe effect of laser frequency and laser power (or temperature)on the diameter distribution of SWCNTs [60]

Scott et al demonstrated the growth mechanism forSWCNTs in a laser ablation process They suggested thatin addition to the carbon obtained from direct ablation ofthe target other substances like carbon particle suspendedin the reaction zone C

2obtained from photodissociation of

fullerenes and other low molecular weight species may alsoserve as feedstock for nanotube growth [61]

Maser et al reported that similar to the arc dischargemethod pressure and composition of the inert gas play asignificant role in laser ablation synthesis and affect the yieldand structural properties of CNTs Both argon andnitrogen ata pressure between 200 and 400 torr resulted in higher yieldof SWCNTs [62] Apart from this factor another importantfactor is the carbon source used Vander Wal et al intheir study replaced the conventional laser-ablation-furnaceapproach with the laser ablation in the flame environmentThe main advantage of this modification is that it gives anenergy efficient approach since a portion of the fuel is burned

to create the elevated temperature while the remainder of thefuel and its incomplete combustion byproducts can serve asthe reactive carbon source for nanotube synthesis [63]

Thus both arc discharge method and laser ablationmethod can be used to produce high quality CNTs Howeverefforts to scale up the process are needed to achieve synthesisof larger quantities with maximum purity

3 Functionalization

Despite of the advantages of CNTs in targeting various typesof cancer cells various constraints have been made on thebiological and biomedical applications of CNTs due to theirlack of solubility in aqueous medium as well as their toxicitycaused by the hydrophobic surface These limitations ofCNTs can be overcome by a process called Functionalization[64] CNT without surface modification are cytotoxic tocertain mammalian cells for example pure MWCNTs caninjure plasma membrane of human macrophages Thereforestrategies for surface functionalization including covalentand noncovalent functionalization are carried out on thesynthesized CNTs [65] The process of functionalization isalso helpful in conjugating the therapeutic molecule or theligands to the CNTs either on the surface or on the endsof CNTs to render them active against cancer cells In thiscontext recently a novel immunologically modified nan-otube system was invented by Chen using glycated chitosan(GC) a potent immunoadjuvant as an effective surfactantfor single-walled carbon nanotubes (SWCNTs) Upon laserirradiation of target tumor cells administration of SWCNT-GC resulted in highly effective tumor suppression in animaltumor models with complete tumor regression and long-term survival in many cases [66] In a study Dai et alused oxidised CNT to covalently link fluorescein or biotin(ligand) allowing the formation of biotin-avidin complexwith fluorescent streptavidin for observing the penetrationpathway of protein-CNT conjugates in the cell [67]

In order to get validated with the modified CNT throughfunctionalization characterization with respect to pristineCNT is necessary to conduct and to ascertain that thedeveloped CNTs possess altered characteristics with respectto functionalization There are several analytical techniqueswhich are used in the chemical and structural charac-terization of modified CNTs [68] IR spectroscopy (func-tional group identification) [69 70] X-ray photoelectronmicroscopy (degree of functionalization) [70 71] electronmicroscopy (structural characterization) [69] Brunauer-Emmett-Teller (BET) analysis (surface area measurement)[72] chemical derivatization (quantification of targeted func-tional group) [73] thermogravimetric analysis (thermal sta-bility and purity evaluation) [74 75] and Raman spec-troscopy (for ascertaining purity defects tube alignment andstructural properties) [76 77] are some reported techniquesused for characterization of CNTs after functionalization

Schematic representation of functionalized CNTs withvarious molecules is given in Figure 4 The functionalizationcan be divided into two main subcategories noncovalentfunctionalization and covalent functionalization


(a)

(b)

(c)(d)

(e)

(f)

(g)(h)

TO

OC

G

C

G

O

O

PO O

A

OO O P

O

OO

O

O

O

HN

OH

NNN NHNH

O O

Glu

3

O

O

O

O

OH

O

n

COOH

COOH

COOH

COOH

COOH

HOOC

HOOC

NO

O

NH

BAm

NH

OO

NH

FITC

O

HN

O

CONH2

OO

O

O O

SNH

NH

N SiH

H

H

HN

HN

O

O FeFe

FeO

OC

HN

O

HN

NH

NHO

NH

O

NH

Figure 4 Schematic illustration of functionalization of CNTs with various molecules (a) Prakash et al [18] (b) Xiao et al [78] (c) Xu et al[70] (d) Gomez-Gualdron et al [64] (e) Bianco et al [79] (f) Jiang et al [80] (g) Williams et al [81] and (h) Kam and Dai [82]

31 Covalent Functionalization Covalent functionalizationof CNTs with the therapeutically active molecule or thebiocompatible surfactants is governed by the oxidation ofCNTs using strong acids (concH

2SO4or concHNO

3) which

generates substitutable hydrophilic functional groups such asCOOH and OH on the CNTs which then further undergointo the chemical reactions such as esterification amidationchlorination bromination hydrogenation and Dielrsquos-Alderreaction In order to get functionalized with these activemolecules CNTs allow side-wall covalent attachment offunctional groups by the addition of radicals nucleophiliccarbenes nitrenes nucleophilic cyclopropanation and elec-trophiles [79 83 84] The method of oxidation results inthe opening of the CNT end caps generating carboxylicgroups suitable for enhancing the solubility of the CNTs withimproved biocompatibility [85] It has been shown that ahighly negative charge developed as a result of the carboxy-lation increases the hydrophilicity of CNTs Covalent linkageof polyethylene glycols increases the hydrophilicity and thesolubility of CNTs in aqueous media as well as increasingthe size which reduces the rate of clearance of CNTs throughthe kidneys and tends to increase the circulation time in theplasma Tour et al proposed the functionalization of CNTsin acidic media which yields oxidized CNTs in large and

industrial scale quantities [86] Side wall functionalizationof SWCNTs through CndashN bond forming substitutions offluoronanotubes was explored by Khabashesku et al andreported that this method offers a wide range of furtherSWCNTs derivatizations including their covalent binding toamino acids DNA and polymer matrix [87]

32 Noncovalent Functionalization Noncovalent functional-ization involves Van derWaals interactions 120587-120587 interactionsand hydrophobic interactions of biocompatible functionalgroups with the surface of the CNT One of the mainadvantages of this type of bonding is the minimal damagecaused to the CNT surface It has been suggested thatnoncovalent attachment preserves the aromatic structure andthus the electronic character as compared to pristine CNTsThis type of functionalization can be done by the additionof hydrophilic polymers biopolymers and surfactants to thewalls of CNTs through weak bonds [88]

A series of anionic cationic and nonionic surfactantshave been already proposed to disperse nanotubes in aqueousmedia Sodium dodecyl sulfate (SDS) and benzylalkoniumchloride are other good examples of surfactants that nonco-valently aggregated to the nanotube side walls and facilitatethe dissolution of CNTs in water The adhesion between


surfactants and nanotube walls becomes very strong due tothe 120587-120587 stacking interactions resulted from the attachment ofaromatic groups of the amphiphile surfactant in the aromaticnetwork of the nanotube side walls as evidenced in the caseof adhesion of N-succinimidyl-1-pyrenebutanoate [89]

In the solubilization of the CNT polymers represent agood alternative to surfactants although they do not havea better dispersion efficiency [90] Amphiphilic polymersor soluble polymers are often used to solubilize CNTsThe main advantage of using polymers instead of smallmolecular surfactants is that the polymers reduce the entropicpenalty of micelle formation Also some conjugated poly-mers have significantly higher energy of interaction withnanotubes than small molecules with nanotubes [91] In thiscontext hydrophilic polymer wraps around the tubes andthus modifies the solubility and conductivity properties ofthe CNTs For example polyvinylpyrrolidone (PVP) havingpolar sides along its long chain assists the dissolution ofPVPSWCNT aggregates in polar solvents Similarly Star etal have substituted poly(metaphenylenevinylene) to suspendSWCNT in organic solvents [92] Biopolymers can also beused for the functionalization of CNTs Nucleic acids arecertainly ideal candidates to form supramolecular complexesbased on 120587-120587 stacking between the aromatic bases and theCNT surface Zhao et al reported the DNA adsorption ona single-walled carbon nanotube (SWCNT) in an aqueousenvironment The hydrophobic end groups of DNA areattracted to the hydrophobic SWCNT surface of unchargedSWCNTs while the hydrophilic backbone of DNA does notbind to the uncharged SWCNT [93] Jiang et al immo-bilized biomolecule bovine serum albumin (BSA) proteinvia two-step process of diimide-activated amidation onMWCTs First carboxylated MWCNTs were activated by N-ethyl-N1015840-(3-dimethylaminopropyl) carbodiimide hydrochlo-ride (EDAC) forming a stable active ester in the presenceof N-hydroxysuccinimide (NHS) Second the active esterwas reacted with the amine groups on the BSA formingan amide bond between the MWNTs and proteins Thistwo-step process avoids the intermolecular conjugation ofproteins and guarantees the uniform attachment of pro-teins on carbon nanotubes [80] William et al developed atechnique to couple SWCNTs covalently to peptide nucleicacid (PNA an uncharged DNA analogue) Ultrasonicallyshortened SWCNT ropes were prepared in a 3 1 mixture ofconcentrated H

2SO4and HNO

3 Subsequent exposure to 1M

HCl produces abundant carboxyl end groups This materialwas then dispersed in dimethyl-formamide (DMF 995)and incubated for 30min in 2mM 1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide hydrochloride and 5mM N-hydroxysuccinimide (NHS) to form SWCNT-bearing NHSesters PNA adducts are formed by reacting this material inDMF for 1 hour with excess PNA [81]

4 Mechanism of CNTs Penetrationinto the Cell

Both types of pure CNTs the single walled and the multi-walled carbon nanotubes have per se no affinity for cells and

also no to cancer cells That means they have to be function-alized in order to make them able to cross the membraneof the normal cells and even more specifically for targetingthem to cancer cells For this reason they are basicallysimilar carriers like liposomes dendrimers or nanoparticlesHowever the advantages of SWCNTs and MWCNTs overother carriers are significant to their hexagonal close-packedcylindrical structure and sp2 hybridization which rendersthem to get easily functionalized with the respective ligandor therapeutic moiety These functionalized CNTs have anability to cross cell membranes but the question arises as tohow these functionalized CNTs can recognize their site ofaction and the route by which they can be delivered to thetarget cell Hence to understand the internalization processCNTs can be tracked by labeling themwith a fluorescent agent(such as fluorescein isothyocyanate) and then monitoringthe uptake by using epifluorescence confocal microscopyand flow cytometry studies [82 94] Additionally detectionof CNTs by nonlabelling methods such as transmissionelectron microscopy (TEM) or atomic force microscopy hasalso been conducted by many researchers Kosuge et aladopted flow cytometry and confocal microscopy to studythe uptake of SWCNTs by the macrophages in murine RAW2647 cells Their observation clearly showed the presence oflabelled SWCNTs inside the cells [95] Transmission electronmicroscopy was conducted by Bonner et al on the murineRAW 2647 cells for the assessment of cellular uptake andsublocalization of MWCNTs TEM results showed that theRAW2647macrophages successfully engulfed theMWCNTs[96] Similarly Sitharaman et al reported the efficacy ofeuropium (Eu) catalyzed SWCNTs (Eu-SWCNTs) as visiblenanoprobes for cellular imaging after observing the internal-ization of Eu-SWCNTs in the breast cancer cells (SK-BR3and MCF-7) via cellular endocyte formation as imaged byconfocal fluorescence microscopy and TEM [97]

To conclude about the exact cellular uptake pathwayof CNTs is complex and it is believed that there are twopossible pathways to cross the cellular membrane (Figure 5)[98] The first is endocytosis dependent pathway which maybe either receptor mediated or nonreceptor mediated andthe second is based on endocytosis independent pathwaywhich includes diffusion membrane fusion or direct poretransport of the extracellular material into the cell [99]The process of internalization of CNTs depends on severalparameters such as the size length nature of functionalgroups hydrophobicity and surface chemistry of CNTs [99100]

Endocytosis dependent pathway is an energy and tem-perature dependent transport process which involves engulf-ing of extracellular materials within a segment of the cellmembrane to form a saccule or a vesicle (hence also calledas corpuscular or vesicular transport) which is then pinchedoff intracellularly into the matrixcytoplasm of the cell [101]Furthermore internalization endocyte formation was shownto be clathrin mediated caveolin-driven endocytosis andthrough macropinocytosis [99] In case of receptor mediatedendocytosis (Figure 5(b)) ligand conjugated-drug loadedCNT binds to the complementary transmembrane receptor


(1)

(2)(4)

(5)

(6)

(3)

(7)(8)

(9)(10)

(11)

(a)

(b)

(c)

Functionalized SWCNTMWCNT


with ligand

Receptor in clathrincaveolin

coated pits


Receptor recycling

Endosomes

Nucleus

Figure 5 Pathways for the penetration of CNTs into the cell (a) Nonreceptor mediated endocytosis (1) membrane that surrounds thedrug loaded functionalized CNTs (2) internalization of drug loaded CNTs and (3) release of drug (b) receptor mediated endocytosis(4) membrane surrounds the CNT-receptor conjugate by forming endosomes followed by internalization (5) release of drug and (6 7 8)regeneration of receptor (c) endocytosis independent pathway (9) direct penetration of drug loaded functionalized CNT and (10) release ofthe drug

proteins and then enters the cell as receptor-ligand complexesin clathrin coated vesicles After internalization vesicles areformed which were known as early endosomes and dueto drop in pH the ligand dissociates from the receptorWhen the receptors are released the vesicles carrying theextracellular particle fuses with lysosomes and thus triggerthe release of the drug particle by the action lysozymeson the endosomes and simultaneously the free receptorsthus formed are being recycled to the plasma membranefor conjugating with other ligand conjugated CNTs [102]An example from the antiangiogenetic area is the targetingof integrin 120572v1205733 which are endothelial cell receptors forextracellular matrix proteins possessing the RGD sequence(arginine-glycine-aspartic acid) and are highly expressedon neovascular endothelial cells Conjugation of RGD pep-tides to nanovectors can lead to higher levels of cellularinternalization and furthermore affect vascular endothe-lial growth factor receptor-2 (VEGFR-2) signalling due tointrinsic association with this signalling pathway leadingto downregulation of the receptor and finally to reducedangiogenesis Another example for active targeting based onligand-receptor interactions relevant to this area of cancertherapeutics is the interaction of folate with its receptorsFolic acid is a vitamin and necessary for the synthesisof nucleotides the DNA building blocks Its counterpart

the folate receptor is significantly upregulated by a broadspectrum of human cancers in some cases by two ordersof magnitude facilitating cellular internalization of folate-conjugated nanovectors by receptor-mediated endocytosisFolate-conjugated nanovectors loaded with anticancer drugshave shown huge potential in overcoming the problem ofmultidrug resistance by evading P-glycoprotein-mediatedefflux which is considered to be a commonproblem in cancerdrug administration [103]

In a study Jhao et al reported the stimulation of Toll-like receptor-9 (TLR9) presented on the intracranial GL261gliomas bearing mice by CpG oligodeoxynucleotide (CpG)conjugated SWCNTs and concluded that functionalizedCNTs were responsible for augmenting CpG prostimulatorfunction by facilitating its uptake through the TLR9 receptormediated endocyte localization into the glioma cells [104]Iancu et al synthesized Human serum albumin (HSA)functionalized MWCNTs inside the malignant liver cells(HepG2 cells) via 60KDa glycoprotein (Gp60 which isknown to function as albumin transcytosis in malignantcells) selective uptake of albumin bounded CNTs by formingan endocyte around it [105] Similarly fluorescein isothy-ocyanate labelled lectin conjugated SWCNTs recognisesN-acetylgalactosamine containing glycoprotein in MCF-7breast cancer cell and internalized into the cell as ligand


mediated endocytosis [106] Dhar et al conjugated cisplatin-platinum (IV) prodrug to amine functionalized SWCNTsthroughmultiple amide linkages and demonstrated its abilityto target folic receptors positive (FR+) tumor cells (humanchoriocarcinoma cells JAR and human nasopharyngeal car-cinoma cells KB) Results obtained from the fluorescencemicroscopy analysis clearly stated the applicability of theconjugated system to selectively target FR+ receptors andthe internalization of the system was through the folic acidreceptor mediated endocytosis [107]

In general the longCNTs (gt1 120583min length)were taken upby the process of phagocytosis (a part of endocytosis) whichwas mainly conducted by the macrophages monocytes andneutrophils while the shorter CNTs (length from a few toseveral hundred nanometers) were mainly internalized bypinocytosis [108] It was found that altering the hydropho-bicity of the CNTs by conjugating them with phospholipidssignificantly alters the uptake of CNTs by the cells as observedby Kapralov et al They compared the internalization of thesurfactant (phosphatidylcholines and phosphatidylglycerols)conjugated SWCNT with pristine SWCNT in the murineRAW 2647 cells and the data obtained from flow cytometricanalysis clearly states that the adsorbed phospholipids sig-nificantly enhanced the uptake of SWCNTs via phagocytosisas phospholipids are known to greatly associate with thephospholipids head group of the cellular membrane incomparison to pristine or uncoated SWCNT [109]

In case of nonreceptor mediated endocytosis(Figure 5(a)) a small portion of the plasma membranesurrounds the drug loaded CNTs and then pinches offintracellularly as an endocyte vesicle The process isgoverned by the intrinsic property of the CNTs as wellas functional groups present on it The endosomes thusformed are eventually converted into the lysosomes andultimately result in the drug release [102] Liu et al developedSWCNT conjugated with paclitaxel (PTX) and reportedthe nonreceptor mediated endocytosis mechanism for thecellular uptake in murine 4T1 breast carcinoma cells [110]

Islam et al investigated the cellular uptake of pluroniccopolymer-stabilized purified sim145 nm long single walledcarbon nanotubes (SWCNTs) through a series of comple-mentary cellular cell-mimetic and in vitromodel membraneexperiments The Raman intensity distribution obtainedfrom the G-band (1590 cmminus1) shows SWCNT concentrationlocalized to the midplane of a fixed hematoxylin-labelledcell SWCNTs were preferentially located within cells versusthe extracellular regions and most SWCNTs were localizedin the perinuclear region SWCNTs localized within fluores-cently labelled endosomes and confocal Raman spectroscopyshowed a dramatic reduction in SWCNT uptake into thehematoxylin-labeled HeLa cell at 4∘C compared with 37∘Cafter being incubated for 2 days These data suggestedenergy-dependent endocytosis To confirm this a directmeasurement to check the endocytosis was conducted inwhich endocytosis in HeLa cells was visualized using a GreenFluorescent Protein GFP-tagged RhoB-GTPase which labelsendosomes in mammalian cells On confocal imaging itwas confirmed that the internalization of SWCNTs was

occurring through the endocyte formation as there was aslight increase in endosome numbers per cell with increasedtime of exposure to SWCNTs with a statistically significantincrease in endosome number at 20 and 25 minutes [111]

In endocytosis independent pathway there is a directtranslocation of CNT through the plasma membrane intothe cytoplasm which has been termed by some researchersas the ldquonanoneedlerdquo mechanism [100] This pathway includesprocesses such as diffusion membrane fusion and directpore transport (Figure 5(c)) Individually dispersed CNTs inaqueous solutions have been experimentally demonstrated tobe able to enter the cytoplasm of cells by directly crossingthe cell membrane Such cellular uptake of CNT whichis not influenced by the presence of endocytosis inhibitor(such as sodiumazide) suggests the endocytosis independentpathway of internalization [112] The mechanism of howCNT enters cells via the insertion and diffusion is poorlyunderstood Some theoretical studies suggest a two-stepprocess in which first the tubes accommodate onto the lipidcell membrane and then orient to adopt the transmembraneconfiguration In this model the internalization of nanotubesinto the cells was spontaneous and was mediated by thelipid membrane and that the hydrophilic interactions andorstatic charge interactions between the tubes and the lipidmembrane which drove the translocation of the nanotubes[113] The conformation of CNT perpendicular to the plasmamembrane during uptake suggested a mechanism similar tonanoneedles which perforate and diffuse through the lipidbilayer of the plasma membrane without inducing cell death[79] Rawson et al reported the first demonstration of adirect interface of vertically aligned SWCNTs (VASWCNTs)with eukaryotic RAW 2647 mouse macrophage cell lineVASWCNTs entered the cells naturally due to its needle-likestructure without application of any external force owing toendocytosis independent pathway for internalization [114]

5 Application of CNTs in Cancer Treatment

For decades human immortal cancer cell lines have con-stituted an accessible easily usable set of biological modelswith which to investigate cancer biology and to explorethe potential efficacy of anticancer drugs is of less tediouswork Currently various ex vivo studies such as cell linestudies cellular uptake studies fluorescent microscopy andflow cytometry are carried out for this purpose

Various cancer cell lines were cultured with modifiedCNTs (functionalization on the surface and ends of the CNTsand by conjugating CNTs with ligands) and evaluated fortherapeutic efficacy cell viability cell survival assays and cellapoptosis Ex vivo studies specifically used in the evaluationof CNTs for cancer chemotherapy are shown in Table 1

51 Brain Cancer Brain cancer is the leading cause ofcancer-related death in the US in patients under the age of35 Anaplastic astrocytomas (Grade III) and glioblastomas(Grade IV) are most aggressive brain cancers with survivalperiod of 24 and 9 months respectively [138] Children whosurvive their brain cancers (mainly medulloblastomas) often

10 Journal of Drug DeliveryTa

ble1Im

pactof

functio

nalized

CNTs

oncancer

celllin

es

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Brain

cancer

MWCN

Tsmdash

mdash

Influ

ence

ofpu

rityand

surfa

ceoxidationon

cytotoxicityof

MWCN

Tswith

human

neurob

lasto

ma

cells

Hum

anneurob

lasto

mac

ell

lineS

H-SY5

Y

With

prolon

gedcultu

reslossof

cell

viabilitywas

minim

alforp

reparatio

nswith

99pu

ritybu

tsignificantadverse

effectswered

etectedwith

97pu

rityand

with

acid

treated

preparationsA

concentrationof

5ndash10120583gmLof

MWCN

Tsseem

sidealforg

enea

nddrug

therapyagainstcancer

[115]

SWCN

Ts

Phosph

olipid-polyethylene

glycol(PEG

)proteinA

fluorescein

labeledintegrin

120572v1205733mAb

mdash

Functio

nalSWCN

Tsbased

onan

integrin120572v1205733mAb

forthe

high

lyeffi

cient

cancer

line

Hum

anU-87M

Gglioblastomac

ell

MCF

-7

Invitro

study

revealed

that

SWCN

T-PE

G-m

Abpresentedah

igh

targetingeffi

ciency

onintegrin

120572v1205733-positive

U87MGcells

with

low

cellu

lartoxicity

[116]

MWCN

TsAng

iopep-2PE

Gylated

Doxorub

icin

Targeted

deliveryof

antic

ancerd

rugs

tobrain

gliomab

yPE

Gylated

oxidized

MWCN

Tsmod

ified

with

angiop

ep-2

C6gliomac

ells

Ang

iopep-2mod

ified

PEGylated

MWCN

Tsshow

edbette

rantiglio

ma

activ

itygoo

dcompatib

ilityand

low

toxicity

[117]

MWCN

TsPo

ly(acrylicacid)a

ndfolic

acid

Doxorub

icin

Dualtargeteddeliveryof

doxorubicinto

cancer

cells

usingfolateconjugated

magnetic

MWCN

Ts

U87

human

glioblastomac

ells

Dualtargetin

gof

doxorubicinfro

mmagnetic

MWCN

Tsshow

edenhanced

cytotoxicitytowardU87

human

glioblastomac

ellscomparedwith

free

doxorubicin

[118]

SWCN

TsCD

133mon

oclonal

antib

ody(m

AB)

mdash

Phototherm

olysisof

glioblastomas

tem

likec

ells

targeted

byCN

Tconjug

ated

with

CD133

mAB

GBM

-CD133+

and

GBM

-CD133minus

cells

GBM

-CD133+

cells

weres

electiv

elytargeted

anderadicated

whereas

CD133minus

cells

remainedviableaft

erincubatio

nwith

SWCN

T-CD

133m

AB

GBM

-CD133+

cells

pretreated

with

SWCN

T-CD

133m

ABandirr

adiatedby

near-in

frared

laserfor

2days

didno

texhibitsustainabilityof

cancer

stem

like

cells

features

fortum

orgrow

th

[119]

MWCN

Tsmdash

SiRN

Aand

DNA

Internalizationof

MWCN

Tsby

microglia

possibleapplicationin

immun

otherapy

ofbrain

tumors

BV2microgliaand

GL261

gliomac

ells

Uptakeo

fMWCN

Tsby

both

BV2and

GL2

61cells

invitro

with

outany

significantsigns

ofcytotoxicity

[120]

Bloo

dcancer

SWCN

TsSgc8ca

ptam

erDauno

rubicin

(Dau)

Reversibletargetingand

controlledreleased

elivery

ofdaun

orub

icin

tocancer

cells

byaptamer-w

rapp

edCN

Ts

Hum

anTcell

leuk

emiacell

MOLT

-4andU266

myelomac

ells

Thetertia

rycomplex

Dau-aptam

er-SWCN

Tswas

internalized

effectiv

elyto

MOLT

-4cells

butn

otto

U266cells

andislesstoxicinU266as

comparedto

Dau-aptam

er-SWCN

Tscomplex

isableto

selectively

target

MOLT

-4cells

[121]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo

dcirculationhalf-lives

thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn

otreceptor-negativeM

CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell

VerticallyalignedMWCN

Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and

potentialcytotoxiceffects

Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic

altargetingcapabilitiestow

ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells

viabilityandfocaladh

esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]


suffer substantial adverse effects related to the toxicities oftherapy on the developing nervous system [139] Currentlyavailable systemic chemotherapy is less effective due topresence of the blood-brain barrier (BBB) which restricts thepenetration of most drugs into the brain Recently a numberof CNT-based targeting approaches have been developed forthe treatment of brain cancer and a brief account is presentedbelow

Vittorio et al investigated the biocompatibility of MWC-NTs with cultured Human neuroblastoma cells SH-SY5YReactive oxygen species (ROS) are chemically reactivemolecules containing oxygen ROS can damage cellularproteins lipids and DNA leading to fatal lesions in cells thatcontribute to carcinogenesis In vitro experiments showedloss of cell viability was minimal with no intracellular ROSdetected with prolonged cultures and continued propagationin the presence of 99 97 pure MWCNTs and acid-treated 97 pureMWCNTs but no significant decrease in theproliferation of cells incubated for 3 days was observed withthe cells cultured with 99 pureMWCNTs After conductingWST-1 assay it was assessed that on increasing the concen-tration of MWCNTs from 5120583gmL to 500120583gmL purity andsurface oxidation of MWCNTs seem to downregulate the cell viability and at 5 120583gmL 100 cells are viable Hence it wasconcluded that the concentration of 5ndash10 120583gmL seems idealfor gene and drug therapy against cancer [115]

Xing et al synthesized phospholipid-bearing polyethy-lene glycol (PL-PEG) functionalized SWCNTs conjugatedwith protein A which was further coupled with thefluorescein-labeled integrin 120572v1205733 monoclonal antibody toform SWCNT-integrin 120572v1205733monoclonal antibody (SWCNT-PEG-mAb) Confocalmicroscopy revealed that SWNT-PEG-mAb showed a much higher fluorescence signal on integrin120572v1205733-positive U87MG cells and presented a high target-ing efficiency with low cellular toxicity while for integrin120572v1205733-negative MCF-7 cells no obvious fluorescence wasobserved which clearly reveals low targeting efficiency ofthe functionalized SWCNTs demonstrating that the specifictargeting of integrin 120572v1205733-positive U87MG cells was causedby the specific recognition of integrin 120572v1205733 on the cellularmembrane by the 120572v1205733 monoclonal antibody [116]

Oxidized MWCNTs cannot only be distributed in thebrain but may accumulate in tumors after conjugating withspecific ligands and also possess an ultrahigh surface area forefficient loading of anticancer drug Ren et al developed adual targeting PEGylatedMWCNTs and loadedwith a target-ing ligand angiopep2 (ANG) and doxorubicin respectivelyto target low density lipoprotein receptor-related proteinreceptor which is overexpressed on the blood brain barrier(BBB) and C6 glioma cells In vitro intracellular tracking andin vivo fluorescence imaging demonstrated the ideal dualtargeting of the developed system which was attained by thehigher transcytosis capacity and parenchymal accumulationby the angiopep-2 and can be considered a material ofchoice to cross blood brain barrier as well as to specificallyrecognise their lipoprotein receptors present on the gliomacells for directing the site specific release of anticancer drugC6 cytotoxicity hematology analysis and CD68 immuno-histochemical analysis reveals better antiglioma effect with

good biocompatibility and low toxicity of O-MWCNTs-PEG-ANG compared with that of free doxorubicin [117]

The existence of cancer stem cells (CSCs) or stem-likecancer cells (SLCCs) is regarded as the cause of tumorformation and their recurrence However the origin of suchcells remains controversial with two competing hypothesesCSCs are either transformed tissue adult stem cells or ded-ifferentiated from transformed progenitor cells [140] Wanget al explored the potential of CD133 monoclonal antibody(anti-CD133) conjugated SWCNTs for therapeutic targetingof CD133 CSCs Glioblastoma (GBM)-CD133+ cells wereselectively targeted and eradicated whereas GBM-CD133minuscells remained viable Furthermore anti-CD133-SWCNTspretreated GBM-CD133+ cells were irradiated with near-infrared laser for 2 days and showed no sign of sustainabilityof CSCs for tumor growth after xenotransplantation in nudemice From this report it is stated that monoclonal antibodyconjugated SWCNTs are capable of selectively targeting theCSCs as well as blocking their recurrence [119]

52 Blood Cancer Leukemia is a cancer that begins in thebonemarrow (the soft inner part of some bones) but in mostcases moves into the blood It can then spread to other partsof the body such as organs and tissues Acute lymphoblasticleukemia (ALL) one of the four main types of leukemia is aslow-growing blood cancer that starts in bone marrow cellscalled lymphocytes or white blood cells Once these whiteblood cells are affected by leukemia they do not go throughtheir normal process of maturingThe lymphocytes continueto reproduce and build up and invade the blood fairly quicklyALL is an aggressive type of leukemia without treatmentmost patients with acute leukemia would live only a fewmonths [141]

An enhanced targeted delivery of daunorubicin (Dau)to acute lymphoblastic leukemia was achieved by Taghdisiet al they developed a tertiary complex of Sgc8c aptamerdaunorubicin and SWCNT named as Dau-aptamer SWC-NTs Flow cytometric analysis showed that the tertiary com-plex was internalized effectively into human T cell leukemiacell (MOLT-4 cells) but not to U266 myeloma cells [121]

53 Breast Cancer Breast cancer (BC) has become the mostcommonmalignancy and the leading cause of cancer-specificdeath in women according to GLOBOCAN 2008 estimates[142] Overexpression of human epidermal growth factorreceptor 2 (HER2) also known as c-erbB-2 or HER2neu isapproximately 20ndash25 responsible for invasive BC Withan increasing understanding of the role of HER2 in tumorproliferation angiogenesis and metastasis novel specialtreatment strategies for this HER2-positive subtype of BChave been validated and are increasingly used in clinicalpractice One of the most important treatment strategies isto block the signal pathway of HER2neu this is defined astargeted therapy [143]

In a study Pan et al investigated the efficiency ofMWCNTs to deliver gene to the tumor cell for cancertherapy In this work they fabricated MWCNTs modified


with polyamidoamine dendrimer which were further con-jugated with FITC-labelled antisense c-myc oligonucleotides(asODN) Human breast cancer cell line MCF-7 cells andMDA-MB-435 cells were incubated with modified MWC-NTs (asODN-dMNTs) Fluorescence developed by the FITCrevealed the cellular uptake of asODN-dMNTswithin 15minThese composites inhibit the cell growth in time and dosedependent means and downregulated the expression of c-myc gene (overexpression of this gene amplify the expressionof HER2) and C-Myc protein [123]

A chemically functionalized SWCNT carrier has beendeveloped for the effective delivery of SiRNA and SiRNA-MDM2 complexes to the breast carcinoma B-Cap-37 cellsResults proved the high efficiency of F-SWCNT in carryingSiRNA to the carcinoma cells and the newF-SWCNT-SiRNA-MDM2 complexes caused 4453 inhibition of proliferatingB-Cap-37 carcinoma cells for 72 hours by downregulating theexpression of c-myc gene [125]

Panchapakesan et al discovered the explosive nature ofSWCNT which can act as a potent therapeutic nanobombagents for killing breast cancer cells In his work he adsorbedwater molecule on the SWCNT which upon exposure tolaser light of 800 nm at light intensities of approximately50ndash200MWcm2 which is sufficient to transform opticalenergy to thermal energy and cause the evaporation of watermolecules which built extreme pressure in SWCNT causingthem to explode in the suspension of human BT-474 breastcancer cells in phosphate buffered saline solution and renderthe cells to death The presence of bubbles around the deadcells revealed the boiling effect caused by SWCNT explosions[126]

A water soluble SWCNT-Paclitaxel (PTX) conjugatehas been developed by conjugating PTX to functionalizedpolyethylene glycol SWCNTs via a cleavable ester bondSWCNT-PTX has been found to be highly efficient in sup-pressing tumor growth when compared with clinical taxol inamurine 4T1 breast cancer cells which has been attributed tothe extended blood circulation (due to PEGylation) and ten-fold higher tumor PTX uptake by SWCNT delivery probablythrough enhanced permeability and retention (EPR) effect[110]

54 Colon Cancer Colorectal cancer is the leading causeof death amongst the men and women worldwide andafflicts more than 135000 patients per year in America Thiscancer has usually been viewed as a homogeneous entityrather than a complex heterogeneous disease developingthrough multiple genetic and epigenetic abnormalities suchas defective DNA mismatch repair (dMMR) and the CpGisland methylator phenotype (CIMP) [144]

Abdolahad et al utilize the vertical arrays of MWCNTsfor entrapping the metastatic human colon adenocarcinomaSW-48 cells and HT-29 cancerous cells Due to the extremedeformability and softness of higher metastatic malignantcells they exhibit higher fraction of entrapment by the ver-tically aligned MWCNTs as compared to the less deformableand rigid lower grades of metastatic cancerous cellsThis new

application ofMWCNTs distinguishes the healthy and highlydeformable cancerous cells more precisely than SWCNTsand also showed better delivery of anticancer drugs to thesecancer cells [127]

Triple functionalized SWCNTs were fabricated with ananticancer drug (Doxorubicin) a monoclonal antibody and afluorescent marker (fluorescein) at the noncompetitive bind-ing sites on the SWCNTs for targeting the cancer cells Con-focal laser microscopy reveals the bovine serum albumin-antibody specific receptor mediated uptake of SWCNTsby the human colon adenocarcinoma cell WiDr cells withsubsequent targeting of doxorubicin intracellularly to thenucleus [128]

55 Liver Cancer Hepatocellular carcinoma (HCC) is ahighly prevalent malignancy especially in Asia Liver cirrho-sis is the strongest predisposing factor for HCC accountingfor approximately 80 of patients with this disease In theUnited States Europe and Japan hepatitis C virus (HCV)infection is the major etiology of liver cirrhosis and HCCHepatitis virus B (HBV) infection however is the leadingcause of HCC development in most Asian countries otherthan Japan In addition to HBV andHCV infection alcoholiccirrhosis and metabolic disorders can also act as risk factorsfor HCC [145] c-Myc is among the most frequently overex-pressed genes in human cancers Overexpression of c-Mycin hepatic cells leads to the development of hepatocellularcarcinoma [146] However an attempt has been made by Panet al to suppress the expression of c-myc gene and C-Mycprotein in the tumor bearing cell

Polyamidoamine dendrimer modified CNTs (dMWC-NTs) were fabricated for the efficient delivery of antisensec-myc oligonucleotide (asODN) into liver cancer cell lineHepG2 cells asODN-dMWCNTs composites were incubatedwith HepG2 cells and confirmed to enter into tumor cellswithin 15min by laser confocalmicroscopyThese compositesinhibited the cell growth in time and dose dependent meansand downregulated the expression of the c-myc gene and C-Myc protein These composites exhibit maximal transfectionefficiencies and inhibition effects on tumor cells when com-pared to CNT-NH

2-asODN and dendrimer (asODN) alone

[123]Meng et al constructed a highly effective targeted DDS

based on chitosan and folic acid modified SWCNTs forcontrollable loadingrelease of anticancer agent doxorubicin(DOX)The obtained DDS not only effectively killed the hep-atocellular carcinoma SMMC-7721 cell lines and depressedthe growth of liver cancer but also displayedmuch less in vivotoxicity than free doxorubicin [129]

56 Lymph Node Metastasis The presence of lymph nodeinvasion is one of the strongest indicators for prognosesof distant metastasis and survival in most cancers In themultistep process of cancermetastasis development invasioninto a vascular or a lymphatic system has generally beenbelieved to be a key step of tumor cell dissemination Oncetumor cells acquire abilities of intravasation and survival inan unfavorable vascular environment they circulate around


the whole body parts to form new tumors at the secondarysite [147] Lymph node metastasis is a powerful predictor ofrecurrence and death in patients with cutaneous melanomaMetastasis to regional lymph nodes develops during thecourse of the disease in approximately 30 of patients withcutaneous melanoma [148]

Yang et al compared the in vitro and in vivo potentialtherapeutic effect of gemcitabine (GEM) loaded magneticMWCNTs (mMWCNTs) with that of gemcitabine loadedmagnetic-carbon particles (mACs) His finding reflects thehigh antitumor activity in human pancreatic cancer BxPC-3 cells of both the systems when compared along with freedrug Due to superparamagnetic behaviour of mMWCNTs-GEM theirmagneticmoments tend to align along the appliedfield leading to net magnetization which greatly affects theinteraction of mMWCNTs-GEMwith the cellular membraneand thus they were found to be superior than mACs-GEM insuccessful inhibition of lymphnodemetastasis after followingsubcutaneous administration under the impact of magneticfield [130]

57 Kidney Cancer Renal cell carcinoma (RCC) is respon-sible for approximately 80 of primary renal cancers andurothelial cell carcinoma (UCC) accounts for the majorityof the remainder (20) The most common histologicalsubtype of RCC is the conventional or clear cell (ccRCC)The occurrence of ccRCC is due to the defunctioning of theVon Hippel-Lindau (VHL) tumor suppressor gene (TSG)located on chromosome 3p Loss of functioning of the VHLprotein leads to stabilization of hypoxia-inducible factors andnuclear transcription factors that in turn can activate thetranscription of many genes including those encoding vas-cular endothelial growth factor (VEGF) and platelet derivedgrowth factor [149] RCC is a highly aggressive tumor and alsothe most lethal of urologic malignancies with an estimated88400 new cases and 39300 kidney cancer-related deathsfrom RCC in Europe [150]

Cui et al investigated the interaction between SWC-NTs and human embryo kidney HEK-293 cells intended toexplore SWCNT biocompatibility and safety It was foundthat SWCNTs can inhibit the proliferation of HEK-293 cellsinduce the cell apoptosis and decrease cell adhesive ability ina time and dose dependentmanner SWCNTs induce changesin the cell cycle which could be attributed to the decreasein the number of cells in the S-phase due to upregulatedexpression of P16 which inhibits the cyclin dependent kinaseactivity of CdK2 CdK4 and CdKr and therefore prevents thecells from entering an S-phase and subsequently arresting thecell cycle in the G1 phase [131]

58 Cervical Cancer Oncogenic human papillomavirus(HPV) has a causal role in nearly all cervical cancers andin many vulvar vaginal penile and oropharyngeal cancersHPV types 16 and 18 are majorly responsible for 70 ofcervical cancers [151] In HPV-associated cancers oncogenicantigens E6 and E7 were overexpressed on the tumor cellsand thus they represent an ideal target for developing

antigen-specific immunotherapy for the control of cervicalcancer [152]

Wu et al developed a novel approach of utilizing naturalbiocompatible polymer chitosan for imaging the tumor cellsIn this assay SWCNTs were modified by chitosan (CHIT)fluorescein isothyocyanate (FITC) This was further conju-gated with folic acid (FA) as mostly cancers cells overexpressfolic acid receptors to construct the functional FITC-CHIT-SWCNT-FA conjugate These novel functionalized SWCNTswere found to be soluble and stable in phosphate buffer salineand can be readily transported inside the human cervicalcarcinoma HeLa cells Combining the intrinsic propertiesof CNTs versatility of chitosan and folic acid FITC-CHIT-SWCNT-FA can be used as potential devices for targetingthe drug into the tumor cells and also for imaging them[134]

Five types of CNTs suspensions were prepared by Zhanget al by dispersing SWCNTs acid-treated SWCNTs MWC-NTs acid treatedMWCNTs and amylose wrapped SWCNTsindividually in water and the influence of these scaffoldson human cervical carcinoma HeLa cells was investigatedby WST-1 assay acridine orangeethidium bromide doublestaining and 111015840-dioctadecyl-333101584031015840 tetramethylindocar-bocyanine perchlorate staining The results indicated thatboth ldquodot likerdquo and ldquodash likerdquo focal adhesion kinases (FAKs)were mainly distributed at the periphery of the cells culturedon SWCNTs and on acid-treated SWCNTs and due to thisthey were found undergoing apoptosis with damaged cellmembrane and condensed chromatin however cells culturedon MWCNTs acid-treated MWCNTs and amylose wrappedSWCNTs were found to be viable which is due to thedistribution of ldquodot likerdquo focal adhesion kinases (FAKs) in thewhole cell body of the cells [135]

59 Prostate Cancer Prostate cancer is a slow growing cancerand early propagation of cancer cells occurs before the diseasebecome clinical Cases of prostate cancer in USA estimates238590 in the year 2013 out of which 29720 cases of deathdue to prostate cancer have been reported in SEER stat factssheet published by National Cancer Institute USA [153]Prostate cancer antigen 3 (PCA3) has been validated as theprincipal molecule associated with prostate cancer (PCa)The PCA3 gene is located on the chromosome 9q21ndash22and was molecularly characterized as the prostate cancer-specific gene highly overexpressed in almost all prostatetumor specimens andPCametastasisHerewe discuss a studyusing human prostate cancer cell line with respect to CNTs[154]

Li et al developed a novel targeting SiRNA deliverysystem by using SWCNTs which was chemically functional-ized with polyethylenimine and bound by DSPE-PEG 2000maleimide for further conjugation with tumor targetingAsn-Gly-Arg (NGR) peptide This novel system efficientlycrosses human prostate cancer cell PC-3 cell membrane invitro and induces more severe apoptosis and suppressionin the proliferating cells The combination of near-infraredphotothermal therapy and RNAi significantly enhanced the


antitumor activity without causing toxicity to other organs[137]

6 Toxicological Assessment of CNTs

Despite of the exciting prospects of CNTs in drug deliverythere are some factors which limit the applications of CNTsPresence of impurities nonuniformity in morphology andstructure large surface area (leads to protein opsonization)hydrophobicity insolubility and tendency of CNTs to bundletogether are some obstacles for their nanomedical applica-tions [23 155]

Another key obstacle is the toxicity of CNTs Entranceinto the body is physical and usually few nanoparticles enterthe body however once there they are persistent due to theirlimited metabolisms so their removal is slow and chroniccumulative health effects are studiedThe underlying mecha-nisms of CNT toxicity include oxidative stress production ofcytokines chemokines and inflammatory responses malig-nant transformation DNA damage and mutation (errors inchromosome number as well as disruption of the mitoticspindle) the formation of granulomas and interstitial fibrosis[156 157]

In view of carcinogenicity of CNTs SWCNTs weredirectly instilled into the lungs of the animals it was foundthat exposure to SWCNTs at a high concentration leads tothe development of granulomas in rodents and a concen-tration of 05mgm3 and 25mgm3 for MWCNTs inducesmicrogranulomas with the inflammation in the alveoli [158ndash160] Similarly in a study by Kanno et al demonstratedthe carcinogenic potential of MWCNT to induce multiplemesothelioma with severe peritoneal adhesion when admin-istered intraperitoneally to p53 heterozygous mice This maybe due to its structural similarities (sizeshape) to asbestosas well as persistency in the organism while in an anotherstudy reported by Takanashi et al and it was stated thatsubcutaneously implanting the MWCNTs in to the rasH2mice did not develop neoplasm [161ndash163]

In view to the inflammatory responses with CNTsMonteiro-Riviere et al exposed human epidermal ker-atinocytes (HEK) to MWCNTs and found that MWCNTinduces the release of proinflammatory cytokine interleukin8 from HEK which indicates the irritation response ontarget epithelial cells [164] Similarly upon subcutaneouslyadministering MWCNT at 01mgkg and 1mgkg showedacute inflammation characterized by vasodilatation edemaformation neutrophil infiltrate tissue damage and alsoelicited hyperalgesic response (as seen by the increase pawwithdrawal of animal) [165] In a study Pons et al investigatedthe immunomodulatory activity of MWCNTs in peripheralblood mononuclear cells (PBMCs) from healthy donors andmite-allergic subjects It was observed that MWCNTs mayeither promote or suppress immune responses with the typeof Toll-like receptor agonist the cells are stimulated withBasal secretion of all TNF-120572 IL-2 IL-5 IL-6 IL-1223p40 orIFN-120574 was not altered by MWCNTs in PBMCs derived fromboth healthy donors and allergic subjects but significantlyincreased in the release of TNF-120572 IL-6 and IL-1223p40 was

observed in PBMCs stimulating the Toll-like receptor (TLR2TLR3 and TLR4) agonist [166]

Among the many toxicity pathways interference withcytoskeleton and fibrous mechanisms cell signalling andmembrane perturbations are some of the effects result-ing from exposure to CNTs [157] In a study exposureof MWCNT to the coculture of SAEC (small airwayepithelial cells) a Type II epithelial cell and HMVEC(human microvascular endothelial cells) increases theVEGFA (vascular endothelial growth factor) soluble adhe-sion molecules (sICAM-1 and sVCAM-1) protein levels aswell as increases the intracellular phospho-NF-120581B phospho-Stat3 and phospho-p38 MAPK (mitogen-activated proteinkinases) which tends to induce multiple changes in theendothelial cell barrier including an increase in reactiveoxygen species actin rearrangement loss of VE-cadherin(vascular endothelial) at the cell surface and an increase inendothelial angiogenic ability [167]

It was reported that length of MWCNTs was found toexert effects on the biomembranes when the distribution ofMWCNTs (3ndash14 120583m length) in RAW264 cells was observedunder a light microscope MWCNTs were located on thesurface of the plasma membrane and a portion of themseemed to be stucked on it which tends to increase thepermeability defects of the plasma membrane lipid bilayerwhile shorter (15 120583m) MWCNTs were significantly less toxic[168 169] In a study interference of CNTs with cytoskeletonwas investigated by Shvedova et al and exposure of cul-tured human epidermal keratinocytes (HaCaT) to SWCNTsinduces oxidative stress and results into loss of cell viabilityindicating that dermal exposure to CNTs may lead to thesealtered skin conditions [170]

Not only bare CNTs showed toxicity but also function-alized CNTs were also reported to cause toxicities as ina study by Tian et al covalently functionalized MWCNTswith carboxylate (COOH) polyethylene glycol (PEG) amine(NH2) side-wall amine (sw-NH

2) andpolyetherimide (PEI)

respectively were screened for toxicity in bronchial epithelialcells and BEAS-2B and TPH-1 cells It was observed thatanionic functionalization (COOH and PEG) decreased theproduction of profibrogenic cytokines and growth factors(including IL-1B Transforming growth factor beta 1 (TGF-B1)and platelet derived growth factor-AA (PDGF-AA)) whileneutral and weak cationic functionalization (NH

2and sw-

NH2) showed intermediary effects In contrast the strongly

cationic PEI functionalized MWCNTs induced biologicaleffects Compared to pristineMWCNTs strong cationic PEI-MWCTs induced significant lung fibrosis while carboxyla-tion significantly decreased the extent of pulmonary fibrosis[171] But the toxicity of f-MWCNTs at varying degreesof carboxylation was assessed by Jain et al in a murinemacrophage RAW 2647 cell line a model for liver Kupffercells Increased in vitro cytotoxicity was found to be directlyproportional to carboxylation density which was associatedwith a concurrent increase in the number of apoptoticcells and production of reactive nitrogen species (RNS) andreactive oxygen species (ROS) [172]

Acid-functionalized SWCNTs induce adverse effects inmurine peritoneal macrophages which were related to the


conversion of microtubule-associated protein light chain3 LC3-I to LC3-II and the accumulation of SWCNTin macrophage lysosomes leading to lysosome membranedestabilization which indicates reduced autophagic degrada-tion [173] Campagnio et al studied the toxicity of PEGylatedSWCNTs in pregnant mice A dose of 10 120583gmouse hasno adverse effects both on embryos and dams but at adose of 30 120583gmouse and teratogenic effects associated withplacental damage were detected both in embryos and dams(dose given as a single bolus or as multiple doses) Hepaticdamage in dams was seen only in the multiple exposuregroups PEGylated SWCNTs reached the conceptus whenadministered early in pregnancy and at later stages it wasdetected in the placenta and the yolk sac but not in embryo[174]

Before the widespread utilization of CNTs in the medicalscience it is important to note that the chronic toxicity ofCNT must be experimentally studied and the appropriatesafeguards must be taken against the possible interactionsamong the CNTs and biological systems

7 Conclusion

CNT represents a novel class of carriers for the delivery ofdrugs in a site specific and target oriented manner CNTspossess extraordinary physical chemical and mechanicalproperties which make them as a potent biological carrierto deliver anticancer drugs Studies have clearly shownthat functionalization of CNT and further derivatizationwith biodegradable polymers render them compatible withbiological systems Due to their unique chemistry hexagonalarrangement of carbon atoms various sites are available forboth covalent and noncovalent functionalization with thetherapeutically active molecule or protein macromoleculeswhich envisaged the potential of CNT as nanocarrier for thesite specific delivery of therapeutic agent including peptidesproteins nucleic acid and other small drug molecules fortargeting various cancer cells These functionalized CNTspossess high propensity to traverse cell membrane either viaendocytosis dependent or independent pathways

Thorough investigations have been performed in thisreview on various synthesis and modification routes for theproduction of purified CNTs and their role in combatingcancer Various ex vivo models based on different cancer celllines were studied to determine the pharmacokinetic andpharmacodynamic parameters of anticancer compoundsthat is being carried by the biocompatible nanosized carbontubes at the targeted site on cancer cells All the observationsand results cited in this review evidently endorse the use-fulness of functionalized CNTs as a potential carrier for theanticancer molecule to target the cancer cell without causingtoxicity to other viable cells Also the usefulness of cell lineshas greatly validated the results for the assessment of in vivotherapeutic and diagnostic efficacy for cancer treatment andreduces the dependency on animal and human models forthe treatment of cancer at the preclinical and clinical studytrial level This compilation of the literature provides usefulinformation to researchers for exploring the further scope ofCNTs in the medical science

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

References

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[2] A M A Elhissi W Ahmed I Ul Hassan V R Dhanak andA DrsquoEmanuele ldquoCarbon nanotubes in cancer therapy and drugdeliveryrdquo Journal of Drug Delivery vol 2012 Article ID 83732710 pages 2012

[3] K Kostarelos L Lacerda C D Partidos M Prato and ABianco ldquoCarbon nanotube-mediated delivery of peptides andgenes to cells translating nanobiotechnology to therapeuticsrdquoJournal of Drug Delivery Science and Technology vol 15 no 1pp 41ndash47 2005

[4] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[5] A G Rinzler J Liu H Dai et al ldquoLarge-scale purification ofsingle-wall carbon nanotubes process product and character-izationrdquo Applied Physics A Materials Science amp Processing vol67 no 1 pp 29ndash37 1998

[6] AM Cassell J A Raymakers J Kong andH Dai ldquoLarge scaleCVD synthesis of single-walled carbon nanotubesrdquoThe Journalof Physical Chemistry B vol 103 no 31 pp 6484ndash6492 1999

[7] P Nikolaev M J Bronikowski R K Bradley et al ldquoGas-phase catalytic growth of single-walled carbon nanotubes fromcarbonmonoxiderdquoChemical Physics Letters vol 313 no 1-2 pp91ndash97 1999

[8] M S Dresselhaus G Dresselhaus and P C Eklund Science ofFullerenes and Carbon Nanotubes Academic Press San DiegoCalif USA 1996

[9] T W Ebbesen and P M Ajayan ldquoLarge-scale synthesis ofcarbon nanotubesrdquoNature vol 358 no 6383 pp 220ndash222 1992

[10] C N Rao and A Govindaraj ldquoCarbon nanotubes fromorganometallic precursorsrdquo Accounts of Chemical Research vol35 no 12 pp 998ndash1007 2002

[11] Z F Ren Z P Huang J W Xu et al ldquoSynthesis of large arraysof well-aligned carbon nanotubes on glassrdquo Science vol 282 no5391 pp 1105ndash1107 1998

[12] Z H Xia P R Guduru and W A Curtin ldquoEnhancingmechanical properties of multiwall carbon nanotubes via 1199041199013interwall bridgingrdquo Physical Review Letters vol 98 no 24Article ID 245501 2007

[13] F S Garmaroudi and R A R Vahdati ldquoFunctionalized CNTsfor delivery of therapeuticsrdquo International Journal of NanoDimension vol 1 no 2 pp 89ndash102 2010

[14] L Serpe Conventional Chemotherapeutic Drug Nanoparticlesfor Cancer Treatment Nanotechnologies for the Life SciencesWiley-VCH Weinheim Germany 2006

[15] K T Nguyen ldquoTargeted nanoparticles for cancer therapypromises and challengesrdquo Journal of NanomedicineampNanotech-nology vol 2 no 5 Article ID 1000103e 2011

[16] M Mahmood A Karmakar A Fejleh et al ldquoSynergisticenhancement of cancer therapy using a combination of carbonnanotubes and anti-tumor drugrdquo Nanomedicine vol 4 no 8pp 883ndash893 2009


[17] M Ferrari ldquoCancer nanotechnology opportunities and chal-lengesrdquo Nature Reviews Cancer vol 5 no 3 pp 161ndash171 2005

[18] S Prakash M Malhotra W Shao C Tomaro-Duchesneauand S Abbasi ldquoPolymeric nanohybrids and functionalizedcarbon nanotubes as drug delivery carriers for cancer therapyrdquoAdvanced Drug Delivery Reviews vol 63 no 14-15 pp 1340ndash1351 2011

[19] G Chashoo S K Singh N A Qazi and A K SaxenaldquoNanoparticle based drug delivery system milestone for cancertherapyrdquo Journal of Biomedical and Pharmaceutical Researchvol 1 no 2 pp 1ndash6 2012

[20] G Gregoriadis ldquoEngineering liposomes for drug deliveryprogress and problemsrdquo Trends in Biotechnology vol 13 no 12pp 527ndash537 1995

[21] F Alexis E M Pridgen R Langer and O C FarokhzadNanoparticle Technologies for Cancer Therapy Springer BerlinGermany 2010

[22] D Peer J M Karp S Hong O C Farokhzad R Margalit andR Langer ldquoNanocarriers as an emerging platform for cancertherapyrdquo Nature Nanotechnology vol 2 no 12 pp 751ndash7602007

[23] P X Hou C Liu and H M Cheng ldquoPurification of carbonnanotubesrdquo Carbon vol 46 no 15 pp 2003ndash2025 2008

[24] J L Zimmerman R K Bradley C B Huffman R H Haugeand J L Margrave ldquoGas-phase purification of single-wallcarbon nanotubesrdquo Chemistry of Materials vol 12 no 5 pp1361ndash1366 2000

[25] H Hu B Zhao M E Itkis and R C Haddon ldquoNitric acidpurification of single-walled carbon nanotubesrdquo The Journal ofPhysical Chemistry B vol 107 no 50 pp 13838ndash13842 2003

[26] S Bandow A M Rao K A Williams A Thess R E Smalleyand P C Eklund ldquoPurification of single-wall carbon nanotubesby microfiltrationrdquoThe Journal of Physical Chemistry B vol 101no 44 pp 8839ndash8842 1997

[27] A P Yu E Bekyarova M E Itkis D Fakhrutdinov R Websterand R C Haddon ldquoApplication of centrifugation to the large-scale purification of electric arc-produced single-walled carbonnanotubesrdquo Journal of the American Chemical Society vol 128no 30 pp 9902ndash9908 2006

[28] W Huang Y Wang G H Luo and F Wei ldquo999 puritymulti-walled carbon nanotubes by vacuum high-temperatureannealingrdquo Carbon vol 41 no 13 pp 2585ndash2590 2003

[29] P X Hou S Bai Q H Yang C Liu and H M Cheng ldquoMulti-step purification of carbon nanotubesrdquo Carbon vol 40 no 1pp 81ndash85 2002

[30] N Sinha and J T W Yeow ldquoCarbon nanotubes for biomedicalapplicationsrdquo IEEE Transactions on Nanobioscience vol 4 no2 pp 180ndash195 2005

[31] B Sitharaman A M DeRosa K Greco and S RajamanildquoRecent patents on single-walled carbon nanotubes for biomed-ical imaging drug delivery and tissue regenerationrdquo RecentPatents on Biomedical Engineering vol 3 no 2 pp 86ndash94 2010

[32] M Ohkohchi Y Ando S Bandow and Y Saito ldquoFormationof carbon nanotubes by evaporation of carbon rod containingscandium oxiderdquo Japanese Journal of Applied Physics vol 32 no9 pp L1248ndashL1251 1993

[33] S-H Jung M-R Kim S-H Jeong et al ldquoHigh-yield synthesisof multi-walled carbon nanotubes by arc discharge in liquidnitrogenrdquoApplied Physics AMaterials Science amp Processing vol76 no 2 pp 285ndash286 2003

[34] M V Antisari R Marazzi and R Krsmanovic ldquoSynthesis ofmultiwall carbon nanotubes by electric arc discharge in liquidenvironmentsrdquo Carbon vol 41 no 12 pp 2393ndash2401 2003

[35] S D Wang M H Chang K M D Lan C C Wu J JCheng and H K Chang ldquoSynthesis of carbon nanotubes byarc discharge in sodium chloride solutionrdquo Carbon vol 43 no8 pp 1792ndash1795 2005

[36] K Anazawa K Shimotani C Manabe H Watanabe and MShimizu ldquoHigh-purity carbon nanotubes synthesis method byan arc discharging in magnetic fieldrdquo Applied Physics Lettersvol 81 no 4 pp 739ndash741 2002

[37] Y Ando X Zhao K Hirahara K Suenaga S Bandow and SIijima ldquoMass production of single-wall carbonnanotubes by thearc plasma jet methodrdquo Chemical Physics Letters vol 323 no 5-6 pp 580ndash585 2000

[38] H Cheng C Liu H Cang M Liu Y Fan and G SuldquoProduction of single-walled carbon nanotubes by a hydrogenarc discharge methodrdquo US Patent 6517800 2003

[39] S Farhat M L de la Chapelle A Loiseau et al ldquoDiametercontrol of single-walled carbon nanotubes using argon-heliummixture gasesrdquoThe Journal of Chemical Physics vol 115 no 14pp 6752ndash6759 2001

[40] H Kajiura Y Liu Y Li et al ldquoSynthesis of single-walled carbonnanotubes by an arc-discharge method using selenium as apromoterrdquo Carbon vol 49 no 14 pp 4792ndash4800 2011

[41] H H Kim and H J Kim ldquoPreparation of carbon nanotubesby DC arc discharge process under reduced pressure in an airatmosphererdquo Materials Science and Engineering B Solid-StateMaterials for Advanced Technology vol 133 no 1ndash3 pp 241ndash2442006

[42] S B Sinnott and R Andrews ldquoCarbon nanotubes synthesisproperties and applicationsrdquo Critical Reviews in Solid State andMaterials Sciences vol 26 no 3 pp 145ndash249 2001

[43] H Dai ldquoCarbon nanotubes opportunities and challengesrdquoSurface Science vol 500 no 1ndash3 pp 218ndash241 2002

[44] M A R Mohd and J Iqbal ldquoProduction of carbon nanotubesby different routesmdasha reviewrdquo Journal of Encapsulation andAdsorption Sciences vol 1 pp 29ndash34 2011

[45] J E Herrera andD E Resasco ldquoRole of Co-W interaction in theselective growth of single-walled carbon nanotubes from COdisproportionationrdquo The Journal of Physical Chemistry B vol107 no 16 pp 3738ndash3746 2003

[46] J-C Charlier H Amara and P Lambin ldquoCatalytically assistedtip growth mechanism for single-wall carbon nanotubesrdquo ACSNano vol 1 no 3 pp 202ndash207 2007

[47] J Gavillet A Loiseau C Journet FWillaime F Ducastelle andJ-C Charlier ldquoRoot-growth mechanism for single-wall carbonnanotubesrdquo Physical Review Letters vol 87 no 27 part 1 ArticleID 275504 2001

[48] P Balbuena J Zhao S Huang Y Wang N Sakulchaicharoenand D E Resasco ldquoRole of the catalyst in the growth ofsingle-wall carbon nanotubesrdquo Journal of Nanoscience andNanotechnology vol 6 no 5 pp 1247ndash1258 2006

[49] S Hofmann M Cantoro S Pisana et al ldquoCatalytic chemicalvapor deposition of single-wall carbon nanotubes at low tem-peraturesrdquo Nano Letters vol 6 no 6 pp 1107ndash1112 2006

[50] M Chen C-M Chen and C-F Chen ldquoPreparation of highyield multi-walled carbon nanotubes by microwave plasmachemical vapor deposition at low temperaturerdquo Journal ofMaterials Science vol 37 no 17 pp 3561ndash3567 2002


[51] Y C Choi D J Bae Y H Lee et al ldquoGrowth of carbonnanotubes by microwave plasma-enhanced chemical vapordeposition at low temperaturerdquo The Journal of Vacuum Scienceand Technology A Vacuum Surfaces and Films vol 18 no 4 pp1864ndash1868 2000

[52] F Huisken R Alexandrescu A Crunteanu et al ldquoSynthesisof carbon nanotubes by CO

2-laser-assisted chemical vapour

depositionrdquo Infrared Physics amp Technology vol 44 no 1 pp 43ndash50 2003

[53] W J Lackey S N Bondi R W Johnson X Wang and Z LWang ldquoLaser assisted chemical vapor deposition synthesis ofcarbon nanotubes and their characterizationrdquo Carbon vol 44no 8 pp 1393ndash1403 2006

[54] A A Khodadadi and Y Mortazavi ldquoCarbon nanotubes contin-uous synthesis process using iron floating catalysts and MgOparticles for CVD of methane in a fluidized bed reactorrdquo USPatent 8293204 2012

[55] H Dai ldquoNanotube growth and characterizationrdquo in CarbonNanotubes vol 80 of Topics in Applied Physics pp 29ndash53Springer Berlin Germany 2001

[56] T Guo P Nikolaev A Thess D T Colbert and R E SmalleyldquoCatalytic growth of single-walledmanotubes by laser vaporiza-tionrdquo Chemical Physics Letters vol 243 no 1-2 pp 49ndash54 1995

[57] A Szabo C Perri A Csato G Girodano D Vuono and JB Nagy ldquoSynthesis methods of carbon nanotubes and relatedmaterialsrdquoMaterials vol 3 no 5 pp 3092ndash3140 2010

[58] W K Maser E Munoz A M Benito et al ldquoProduction ofhigh-density single-walled nanotube material by a simple laser-ablationmethodrdquoChemical Physics Letters vol 292 no 4ndash6 pp587ndash593 1998

[59] M Yudasaka T Ichihashi T Komatsu and S Iijima ldquoSingle-wall carbon nanotubes formed by a single laser-beam pulserdquoChemical Physics Letters vol 299 no 1 pp 91ndash96 1999

[60] H Zhang K Chen Y He et al ldquoFormation and Ramanspectroscopy of single wall carbon nanotubes synthesized byCO2continuous laser vaporizationrdquoThe Journal of Physics and

Chemistry of Solids vol 62 no 11 pp 2007ndash2010 2001[61] C D Scott S Arepalli P Nikolaev and R E Smalley

ldquoGrowth mechanisms for single-wall carbon nanotubes in alaser-ablation processrdquo Applied Physics A Materials Science ampProcessing vol 72 no 5 pp 573ndash580 2001

[62] W K Maser E Munoz A M Benito et al ldquoGas and pressureeffects on the production of single-walled carbon nanotubes bylaser ablationrdquo Carbon vol 38 no 10 pp 1445ndash1451 2000

[63] R L Vander Wal G M Berger and T M Ticich ldquoCarbonnanotube synthesis in a flame using laser ablation for in situcatalyst generationrdquo Applied Physics A Materials Science ampProcessing vol 77 no 7 pp 885ndash889 2003

[64] D A Gomez-Gualdron J C Burgos J Yu and P B Bal-buena ldquoCarbon nanotubes engineering biomedical applica-tionsrdquo Progress in Molecular Biology and Translational Sciencevol 104 pp 175ndash245 2011

[65] S Ye Y Jiang H Zhang et al ldquoModulation of apoptotic path-ways of macrophages by surface-functionalized multi-walledcarbon nanotubesrdquo PLoS ONE vol 8 no 6 article e65756 2013

[66] W R Chen ldquoImmunologically modified carbon nanotubes forcancer treatmentrdquo US Patent 20130172848 2013

[67] N W S Kam T C Jessop P A Wender and H DaildquoNanotube molecular transporters internalization of carbonnanotube-protein conjugates into mammalian cellsrdquo Journal ofthe American Chemical Society vol 126 no 22 pp 6850ndash68512004

[68] K A Wepasnick B A Smith J L Bitter and D Howard Fair-brother ldquoChemical and structural characterization of carbonnanotube surfacesrdquoAnalytical and Bioanalytical Chemistry vol396 no 3 pp 1003ndash1014 2010

[69] C Branca F Frusteri V Magazu and A Mangione ldquoChar-acterization of carbon nanotubes by TEM and infrared spec-troscopyrdquo The Journal of Physical Chemistry B vol 108 no 11pp 3469ndash3473 2004

[70] P Xu D Cui B Pan et al ldquoA facile strategy for covalentbinding of nanoparticles onto carbon nanotubesrdquo AppliedSurface Science vol 254 no 16 pp 5236ndash5240 2008

[71] T I T Okpalugo P Papakonstantinou HMurphy J McLaugh-lin and NM D Brown ldquoHigh resolution XPS characterizationof chemical functionalised MWCNTs and SWCNTsrdquo Carbonvol 43 no 1 pp 153ndash161 2005

[72] A Peigney C Laurent E Flahaut R R Bacsa and A RoussetldquoSpecific surface area of carbon nanotubes and bundles ofcarbon nanotubesrdquo Carbon vol 39 no 4 pp 507ndash514 2001

[73] Y Xing N Dementev and E Borguet ldquoChemical labelingfor quantitative characterization of surface chemistryrdquo CurrentOpinion in Solid State and Materials Science vol 11 no 5-6 pp86ndash91 2007

[74] J P Trigueiro G G Silva R L Lavall et al ldquoPurity evaluationof carbon nanotube materials by thermogravimetric TEM andSEMmethodsrdquo Journal of Nanoscience andNanotechnology vol7 no 10 pp 3477ndash3486 2007

[75] L S K Pang J D Saxby and S P Chatfield ldquoThermogravimet-ric analysis of carbon nanotubes and nanoparticlesrdquoThe Journalof Physical Chemistry vol 97 no 27 pp 6941ndash6942 1993

[76] J H Lehman M Terrones E Mansfield K E Hurst and VMeunier ldquoEvaluating the characteristics of multiwall carbonnanotubesrdquo Carbon vol 49 no 8 pp 2581ndash2602 2011

[77] M S Dresselhaus A Jorio A G Souza Filho and R SaitoldquoDefect characterization in graphene and carbon nanotubesusing Raman spectroscopyrdquo Philosophical Transactions of theRoyal Society A vol 368 no 1932 pp 5355ndash5377 2010

[78] Y Xiao X Gao O Taratula et al ldquoAnti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detectionand selective destruction of breast cancer cellsrdquo BMC Cancervol 9 article 351 2009

[79] A Bianco K Kostarelos and M Prato ldquoApplications of carbonnanotubes in drug deliveryrdquo Current Opinion in ChemicalBiology vol 9 no 6 pp 674ndash679 2005

[80] K Jiang L S Schadler R W Siegel X Zhang H Zhang andM Terrones ldquoProtein immobilization on carbon nanotubes viaa two-step process of diimide-activated amidationrdquo Journal ofMaterials Chemistry vol 14 no 1 pp 37ndash39 2004

[81] K A Williams P T M Veenhuizen B G V de la Torre REritja andCDekker ldquoNanotechnology carbonnanotubeswithDNA recognitionrdquoNature vol 420 no 6917 pp 761ndash762 2002

[82] N W S Kam and H Dai ldquoSingle walled carbon nanotubes fortransport and delivery of biological cargosrdquoPhysica Status SolidiB vol 243 no 13 pp 3561ndash3566 2006

[83] M Holzinger O Vostrowsky A Hirsch et al ldquoSidewall func-tionalization of carbon nanotubesrdquo Angewandte Chemie vol40 no 21 pp 4002ndash4005 2001

[84] A Hirsch ldquoFunctionalization of single-walled carbon nan-otubesrdquoAngewandte Chemie vol 41 no 11 pp 1853ndash1859 2002

[85] M A Hamon J Chen H Hu et al ldquoDissolution of single-walled carbon nanotubesrdquo Advanced Materials vol 11 no 10pp 834ndash840 1999


[86] J M Tour J L Hudson C R Dyke and J J StephensonldquoFunctionalization of carbon nanotubes in acidic mediardquo USPatent 20070280876 2007

[87] VN KhabasheskuM LMargrave J L Stevens et al ldquoSidewallfunctionalization of single-wall carbon nanotubes through C-N bending forming substitution of fluoronanotubesrdquo US Patent7452519 2008

[88] Z Liu X Sun N Nakayama-Ratchford and H DaildquoSupramolecular chemistry on water-soluble carbon nanotubesfor drug loading and deliveryrdquo ACS Nano vol 1 no 1 pp50ndash56 2007

[89] A Villaverde Nanoparticles in Translational Science andMedicine Academic Press London UK 2011

[90] T Minko ldquoSoluble polymer conjugates for drug deliveryrdquo DrugDiscovery Today Technologies vol 2 no 1 pp 15ndash20 2005

[91] C Y Hu Y J Xu S W Duo R F Zhang and M S Li ldquoNon-covalent functionalization of carbonnanotubeswith surfactantsand polymersrdquo Journal of the Chinese Chemical Society vol 56no 2 pp 234ndash239 2009

[92] A Star J F Stoddart D Steuerman et al ldquoPreparationand properties of polymer-wrapped single-walled carbon nan-otubesrdquo Angewandte Chemie vol 40 no 9 pp 1721ndash1725 2001

[93] X Zhao and J K Johnson ldquoSimulation of adsorption ofDNAoncarbon nanotubesrdquo Journal of the American Chemical Societyvol 129 no 34 pp 10438ndash10445 2007

[94] D Pantarotto J-P Briand M Prato and A Bianco ldquoTranslo-cation of bioactive peptides across cell membranes by carbonnanotubesrdquo Chemical Communications no 1 pp 16ndash17 2004

[95] H Kosuge S P Sherlock T Kitagawa et al ldquoNear Infraredimaging and photothermal ablation of vascular inflammationusing single-walled carbon nanotubesrdquo Journal of the AmericanHeart Association vol 1 no 6 Article ID e002568 2012

[96] J C Bonner J K Lee B C Sayers et al ldquoMulti-walledcarbonnanotubes induceCOX-2 and iNOS expression viaMAPKinase-dependent and independent mechanisms in mouseRAW2647 macrophagesrdquo Particle and Fibre Toxicology vol 9article 14 2012

[97] B Sitharaman and P K Avti ldquoLuminescent single-walledcarbon nanotube-sensitized europium nanoprobes for cellularimagingrdquo International Journal of Nanomedicine vol 7 pp1953ndash1964 2012

[98] Y Lee and K E Geckeler ldquoCarbon nanotubes in the biologicalinterphase the relevance of noncovalencerdquoAdvancedMaterialsvol 22 no 36 pp 4076ndash4083 2010

[99] C Fisher A E Rider Z J Han et al ldquoApplications and nan-otoxicity of carbon nanotubes and graphene in biomedicinerdquoJournal of Nanomaterials vol 2012 Article ID 315185 19 pages2012

[100] K Kostarelos A Bianco L Lacerda et al ldquoTranslocationmechanisms of chemically functionalised carbon nanotubesacross plasma membranesrdquo Biomaterials vol 33 no 11 pp3334ndash3343 2012

[101] Q Mu D L Broughton and B Yan ldquoEndosomal leakageand nuclear translocation of multiwalled carbon nanotubesdeveloping a model for cell uptakerdquo Nano Letters vol 9 no 12pp 4370ndash4375 2009

[102] B Alberts A Johnson J Lewis M Raff K Roberts and PWalter ldquoTransport into the cell from the plasma membraneendocytosisrdquo inMolecular Biology of the Cell Garland ScienceNew York NY USA 4th edition 2002

[103] R Klingeler and R B Sim Carbon Nanotubes for BiomedicalApplications Springer Berlin Germany 2011

[104] D Zhao D Alizadeh L Zhang et al ldquoCarbon nanotubesenhance CpG uptake and potentiate antiglioma immunityrdquoClinical Cancer Research vol 17 no 4 pp 771ndash782 2011

[105] C Iancu L Mocan C Bele et al ldquoEnhanced laser thermalablation for the in vitro treatment of liver cancer by specificdelivery of multiwalled carbon nanotubes functionalized withhuman serum albuminrdquo International Journal of Nanomedicinevol 6 no 1 pp 129ndash141 2011

[106] S Y Madani A Tan M Dwek and A M Seifalian ldquoFunction-alization of single-walled carbonnanotubes and their binding tocancer cellsrdquo International Journal of Nanomedicine vol 7 pp905ndash914 2012

[107] S Dhar Z Liu J Thomale H Dai and S J Lippard ldquoTargetedsingle-wall carbon nanotube-mediated Pt(IV) prodrug deliveryusing folate as a homing devicerdquo Journal of the AmericanChemical Society vol 130 no 34 pp 11467ndash11476 2008

[108] F Zhao Y Zhao Y Liu X Chang C Chen and Y ZhaoldquoCellular uptake intracellular trafficking and cytotoxicity ofnanomaterialsrdquo Small vol 7 no 10 pp 1322ndash1337 2011

[109] A A Kapralov W H Feng A A Amoscato et al ldquoAdsorptionof surfactant lipids by single-walled carbon nanotubes inmouse lung upon pharyngeal aspiration role in uptake bymacrophagesrdquo ACS Nano vol 6 no 5 pp 4147ndash4156 2012

[110] Z Liu K Chen C Davis et al ldquoDrug delivery with carbonnanotubes for in vivo cancer treatmentrdquo Cancer Research vol68 no 16 pp 6652ndash6660 2008

[111] P N Yaron B D Holt P A Short M Losche M F Islamand K N Dahl ldquoSingle wall carbon nanotubes enter cellsby endocytosis and not membrane penetrationrdquo Journal ofNanobiotechnology vol 9 article 45 15 pages 2011

[112] K Kostarelos L Lacerda G Pastorin et al ldquoCellular uptake offunctionalized carbon nanotubes is independent of functionalgroup and cell typerdquo Nature Nanotechnology vol 2 no 2 pp108ndash113 2007

[113] P A Tran L Zhang and T J Webster ldquoCarbon nanofibers andcarbon nanotubes in regenerative medicinerdquo Advanced DrugDelivery Reviews vol 61 no 12 pp 1097ndash1114 2009

[114] F J Rawson C L Yeung S K Jackson and P M MendesldquoTailoring 3D single-walled carbon nanotubes anchored toindium tin oxide for natural cellular uptake and intracellularsensingrdquo Nano Letters vol 13 no 1 pp 1ndash8 2013

[115] O Vittorio V Raffa and A Cuschieri ldquoInfluence of purityand surface oxidation on cytotoxicity of multiwalled carbonnanotubes with human neuroblastoma cellsrdquo NanomedicineNanotechnology Biology and Medicine vol 5 no 4 pp 424ndash431 2009

[116] D Xing Z Ou B Wu F Zhou H Wang and Y TangldquoFunctional single-walled carbon nanotubes based on an inte-grin 120572

1199071205733monoclonal antibody for highly efficient cancer cell

targetingrdquo Nanotechnology vol 20 no 3 Article ID 105102 7pages 2009

[117] J Ren S Shen D Wang et al ldquoThe targeted delivery ofanticancer drugs to brain glioma by PEGylated oxidized multi-walled carbon nanotubes modified with angiopep-2rdquo Biomate-rials vol 33 no 11 pp 3324ndash3333 2012

[118] Y-J Lu K-C Wei C-C Ma S-Y Yang and J-P Chen ldquoDualtargeted delivery of doxorubicin to cancer cells using folate-conjugated magnetic multi-walled carbon nanotubesrdquo Colloidsand Surfaces B Biointerfaces vol 89 no 1 pp 1ndash9 2012


[119] C-H Wang S-H Chiou C-P Chou Y-C Chen Y-J Huangand C-A Peng ldquoPhotothermolysis of glioblastoma stem-likecells targeted by carbon nanotubes conjugated with CD133monoclonal antibodyrdquo Nanomedicine Nanotechnology Biologyand Medicine vol 7 no 1 pp 69ndash79 2011

[120] B Kateb M van Handel L Zhang M J Bronikowski HManohara and B Badie ldquoInternalization of MWCNTs bymicroglia possible application in immunotherapy of braintumorsrdquo NeuroImage vol 37 supplement 1 pp S9ndashS17 2007

[121] SMTaghdisi P LavaeeMRamezani andKAbnous ldquoRevers-ible targeting and controlled release delivery of daunorubicin tocancer cells by aptamer-wrapped carbon nanotubesrdquo EuropeanJournal of Pharmaceutics and Biopharmaceutics vol 77 no 2pp 200ndash206 2011

[122] X Liu H Tao K Yang S Zhang S-T Lee and Z LiuldquoOptimization of surface chemistry on single-walled carbonnanotubes for in vivo photothermal ablation of tumorsrdquo Bioma-terials vol 32 no 1 pp 144ndash151 2011

[123] B Pan D Cui P Xu et al ldquoSynthesis and characterizationof polyamidoamine dendrimer-coated multi-walled carbonnanotubes and their application in gene delivery systemsrdquoNanotechnology vol 20 no 12 Article ID 125101 pp 1ndash9 2009

[124] K Teker ldquoBioconjugated carbon nanotubes for targeting cancerbiomarkersrdquo Materials Science and Engineering B Solid-StateMaterials for Advanced Technology vol 153 no 1ndash3 pp 83ndash872008

[125] H Chen X Ma Z Li et al ldquoFunctionalization of single-walled carbon nanotubes enables efficient intracellular deliveryof siRNA targetingMDM2 to inhibit breast cancer cells growthrdquoBiomedicine amp Pharmacotherapy vol 66 no 5 pp 334ndash3382012

[126] B Panchapakesan S Lu K Sivakumar K Teker G Cesaroneand E Wickstrom ldquoSingle-wall carbon nanotube nanobombagents for killing breast cancer cellsrdquo Nanobiotechnology vol 1no 2 pp 133ndash139 2005

[127] M Abdolahad Z Sanaee M Janmaleki S MohajerzadehM Abdollahi and M Mehran ldquoVertically aligned multiwall-carbon nanotubes to preferentially entrap highly metastaticcancerous cellsrdquo Carbon vol 50 no 5 pp 2010ndash2017 2012

[128] E Heister V Neves C Tılmaciu et al ldquoTriple functionalisationof single-walled carbon nanotubes with doxorubicin a mono-clonal antibody and a fluorescent marker for targeted cancertherapyrdquo Carbon vol 47 no 9 pp 2152ndash2160 2009

[129] L Meng Z Ji G Lin et al ldquoTargeted therapy of SMMC-7721liver cancer in vitro and in vivo with carbon nanotubes baseddrug delivery systemrdquo Journal of Colloid and Interface Sciencevol 365 no 1 pp 143ndash149 2012

[130] F Yang C Jin D Yang et al ldquoMagnetic functionalised carbonnanotubes as drug vehicles for cancer lymph node metastasistreatmentrdquo European Journal of Cancer vol 47 no 12 pp 1873ndash1882 2011

[131] D Cui F Tian C S Ozkan M Wang and H Gao ldquoEffectof single wall carbon nanotubes on human HEK293 cellsrdquoToxicology Letters vol 155 no 1 pp 73ndash85 2005

[132] G M do Nascimento R C de Oliveira N A Pradie et alldquoSingle-wall carbon nanotubesmodifiedwith organic dyes syn-thesis characterization and potential cytotoxic effectsrdquo Journalof Photochemistry and Photobiology A Chemistry vol 211 no2-3 pp 99ndash107 2010

[133] B Wu Z Ou and D Xing ldquoFunctional single-walled carbonnanotubeschitosan conjugate for tumor cells targetingrdquo in 8th

International Conference on Photonics and Imaging in Biologyand Medicine (PIBM rsquo09) vol 7519 of Proceedings of SPIE pp75190K1ndash75190K8 Wuhan China August 2009

[134] R Li R Wu L Zhao et al ldquoFolate and iron difunctionalizedmultiwall carbon nanotubes as dual-targeted drug nanocarrierto cancer cellsrdquo Carbon vol 49 no 5 pp 1797ndash1805 2011

[135] X Zhang X Wang Q Lu and C Fu ldquoInfluence of carbonnanotube scaffolds on human cervical carcinoma HeLa cellviability and focal adhesion kinase expressionrdquo Carbon vol 46no 3 pp 453ndash460 2008

[136] X Zhang L Meng Q Lu Z Fei and P J Dyson ldquoTargeteddelivery and controlled release of doxorubicin to cancer cellsusingmodified single wall carbon nanotubesrdquo Biomaterials vol30 no 30 pp 6041ndash6047 2009

[137] L Wang J Shi H Zhang et al ldquoSynergistic anticancer effectof RNAi and photothermal therapy mediated by functionalizedsingle-walled carbon nanotubesrdquo Biomaterials vol 34 no 1 pp262ndash274 2013

[138] WGeldenhuys TMbimba T Bui K Harrison andV SutariyaldquoBrain-targeted delivery of paclitaxel using glutathione-coatednanoparticles for brain cancersrdquo Journal of Drug Targeting vol19 no 9 pp 837ndash845 2011

[139] J T Huse and E C Holland ldquoTargeting brain cancer advancesin the molecular pathology of malignant glioma and medul-loblastomardquo Nature Reviews Cancer vol 10 no 5 pp 319ndash3312010

[140] Y Liang Z Zhong Y Huang et al ldquoStem-like cancer cells areinducible by increasing genomic instability in cancer cellsrdquoTheJournal of Biological Chemistry vol 285 no 7 pp 4931ndash49402010

[141] American Cancer Society ldquoWhat is Acute LymphocyticLeukemiardquo httpwwwcancerorgcancerleukemia-acutelymphocyticallinadultsdetailedguideleukemia-acute-lymphocytic-what-is-all

[142] J Ferlay H R Shin F Bray D Forman C Mathers and DM Parkin ldquoEstimates of worldwide burden of cancer in 2008GLOBOCAN2008rdquo International Journal of Cancer vol 127 no12 pp 2893ndash2917 2010

[143] T Qin Z Yuan R Peng et al ldquoHER2-positive breast cancerpatients receiving trastuzumab treatment obtain prognosiscomparable with that of HER2-negative breast cancer patientsrdquoOncoTargets and Therapy vol 6 pp 341ndash347 2013

[144] M Donada S Bonin R Barbazza D Pettirosso and Gstanta ldquoManagement of stage II colon cancermdashthe use ofmolecular biomarkers for adjuvant therapy decisionrdquo BMCGastroenterology vol 13 article 36 2013

[145] C-L Teng W-L Hwang Y-J Chen K-H Chang and S-B Cheng ldquoSorafenib for hepatocellular carcinoma patientsbeyond Milan criteria after orthotopic liver transplantation acase control studyrdquo World Journal of Surgical Oncology vol 10article 41 2012

[146] C P Lin C R Liu C N Lee et al ldquoTargeting c-Myc as anovel approach for hepatocellular carcinomardquoWorld Journal ofHepatology vol 2 no 1 pp 16ndash20 2010

[147] S Kim H Nam and D Lee ldquoExploring molecular linksbetween lymph node invasion and cancer prognosis in humanbreast cancerrdquoBMCSystemsBiology vol 5 supplement 2 articleS4 14 pages 2011

[148] N Mozzillo C Caraco U Marone et al ldquoSuperficial anddeep lymph node dissection for stage III cutaneous melanomaclinical outcome and prognostic factorsrdquo World Journal ofSurgical Oncology vol 11 article 36 2013


[149] N V Vasudev P J Selby and R E Banks ldquoRenal cancerbiomarkers the promise of personalized carerdquo BMC Medicinevol 10 article 112 2012

[150] J Ferlay D M Parkin and E Steliarova-Foucher ldquoEstimates ofcancer incidence and mortality in Europe in 2008rdquo EuropeanJournal of Cancer vol 46 no 4 pp 765ndash781 2010

[151] ldquoHuman PapillomavirusmdashAssociated CancersmdashUnited States2004ndash2008rdquo American Journal of Transplantation vol 12 no 7pp 1945ndash1949 2012

[152] A Wu Q Zeng T H Kang et al ldquoInnovative DNA vaccinefor human papillomavirus (HPV)-associated head and neckcancerrdquo Gene Therapy vol 18 no 3 pp 304ndash312 2011

[153] SEER Stat Fact Sheets Prostate Cancer httpseercancergovstatfactshtmlprosthtml

[154] A F Neves J D Dias-Oliveira T G Araujo KMarangoni andL R Goulart ldquoProstate cancer antigen 3 (PCA3) RNAdetectionin blood and tissue samples for prostate cancer diagnosisrdquoClinical Chemistry and Laboratory Medicine vol 51 no 4 pp881ndash887 2013

[155] W Zhang Z Zhang and Y Zhang ldquoThe application of carbonnanotubes in target drug delivery systems for cancer therapiesrdquoNanoscale Research Letters vol 6 article 555 2011

[156] Y Liu Y Zhao B Sun andCChen ldquoUnderstanding the toxicityof carbon nanotubesrdquo Accounts of Chemical Research vol 46no 3 pp 702ndash713 2013

[157] Y Rodriguez-Yanez B Munoz and A Albores ldquoMechanismsof toxicity by carbon nanotubesrdquo Toxicology Mechanisms andMethods vol 23 no 3 pp 178ndash195 2013

[158] C-W Lam J T James R McCluskey and R L HunterldquoPulmonary toxicity of single-wall carbon nanotubes in mice7 and 90 days after intractracheal instillationrdquo ToxicologicalSciences vol 77 no 1 pp 126ndash134 2004

[159] L Ma-Hock V Strauss S Treumann et al ldquoComparativeinhalation toxicity of multi-wall carbon nanotubes graphenegraphite nanoplatelets and low surface carbon blackrdquo Particleand Fibre Toxicology vol 10 no 1 article 23 2013

[160] D B Warheit B R Laurence K L Reed D H Roach GA M Reynolds and T R Webb ldquoComparative pulmonarytoxicity assessment of single-wall carbon nanotubes in ratsrdquoToxicological Sciences vol 77 no 1 pp 117ndash125 2004

[161] J KannoA Takagi AHirose et al ldquoInduction ofmesotheliomain p53+- mouse by intraperitoneal application of multi-wallcarbon nanotuberdquoThe Journal of Toxicological Sciences vol 33no 1 pp 105ndash116 2008

[162] S Takanashi K Hara K Aoki et al ldquoCarcinogenicity evalua-tion for the application of carbon nanotubes as biomaterials inrasH2 micerdquo Scientific Reports vol 2 article 498 2012

[163] K Donaldson C A Poland F A Murphy M MacFarlaneT Chernova and A Schinwalda ldquoPulmonary toxicity ofcarbon nanotubes and asbestosmdashsimilarities and differencesrdquoAdvanced Drug Delivery Reviews vol 65 no 15 pp 2078ndash20682013

[164] N A Monteiro-Riviere R J Nemanich A O Inman YY Wang and J E Riviere ldquoMulti-walled carbon nanotubeinteractions with human epidermal keratinocytesrdquo ToxicologyLetters vol 155 no 3 pp 377ndash384 2005

[165] N V Pinto N F de Andrade D S Martinez et al ldquoInflamma-tory and hyperalgesic effects of oxidized multi-walled carbonnanotubes in ratsrdquo Journal of Nanoscience and Nanotechnologyvol 13 no 8 pp 5276ndash5282 2013

[166] F Pons G Laverny A Casset et al ldquoImmunomodulatoryproperties of multi-walled carbon nanotubes in peripheralblood mononuclear cells from healthy subjects and allergicpatientsrdquo Toxicology Letters vol 217 no 2 pp 91ndash101 2013

[167] B N Snyder-Talkington D Schwegler-Berry V Castranova YQian and N L Guo ldquoMulti-walled carbon nanotubes inducehumanmicrovascular endothelial cellular effects in an alveolar-capillary co-culture with small airway epithelial cellsrdquo Particleand Fibre Toxicology vol 10 article 35 2013

[168] K Shimizu A Uchiyama M Yamashita et al ldquoBiomembranedamage caused by exposure to multi walled carbon nanotubesrdquoThe Journal of Toxicological Sciences vol 38 no 1 pp 7ndash12 2013

[169] D Liu L Wang Z Wang and A Cuschieri ldquoDifferent cellularresponsemechanisms contribute to the length-dependent cyto-toxicity of multi-walled carbon nanotubesrdquo Nanoscale ResearchLetters vol 7 no 1 article 361 2012

[170] A A Shvedova V Castranova E R Kisin et al ldquoExposure tocarbon nanotube material assessment of nanotube cytotoxicityusing human keratinocyte cellsrdquo Journal of Toxicology andEnvironmental Health A vol 66 no 20 pp 1909ndash1926 2003

[171] X Tian R Li X Wang et al ldquoSurface charge and cellularprocessing of covalently functionalized multiwall carbon nan-otubes determine pulmonary toxicityrdquo ACS Nano vol 7 no 3pp 2352ndash2368 2013

[172] S Jain R P Singh M Das and V Thakare ldquoFunctionalizationdensity dependent toxicity of oxidized multiwalled carbonnanotubes in amurinemacrophage cell linerdquoChemical Researchin Toxicology vol 25 no 10 pp 2127ndash2137 2012

[173] B Wan Z X Wang Q Y Lv et al ldquoSingle-walled car-bon nanotubes and graphene oxides induce autophagosomeaccumulation and lysosome impairment in primarily culturedmurine peritoneal macrophagesrdquo Toxicology Letters vol 221no 2 pp 118ndash127 2013

[174] L Campagnolo M Massimiani G Palmieri et al ldquoBiodistri-bution and toxicity of pegylated single wall carbon nanotubesin pregnant micerdquo Particle and Fibre Toxicology vol 10 no 1article 21 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

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Drug DeliveryJournal of



Advances in Pharmacological Sciences

Tropical MedicineJournal of


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AddictionJournal of



BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Autoimmune Diseases


Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of


Pharmaceutics


MEDIATORSINFLAMMATION

of


04ndash30nm

200

ndash10000

nm

(a)

10ndash30nm

20ndash1000 nm

(b)

Figure 1 Carbon nanotube (a) single walled carbon nanotube and (b) multiwalled carbon nanotube

possibleTherefore significant amounts of research have beencarried out to overcome these problems The main problemincurred with various chemotherapies for treating cancer islack of selectivity of the anticancer drug towards cancerouscells This nonspecificity of the drug limits the therapeuticdosewithin cancer cells while providing excessive toxicities tonormal cells tissues and organs and thereby causing severaladverse effects Besides precise tumor targeting and toxicityconcerns drug resistance remains a major obstacle for thetreatment of advanced cancerous tumor [14ndash16] ldquoCancernanotechnologyrdquo is the novel emerging field which usednanocarriers like liposome polymeric nanoparticles den-drimers quantum dots polymersomes carbon nanotubesand so forth for delivering drugs to the target site and thusholds tremendous potential to overcome several problemsassociated with the conventional therapies [17 18] Apartfrom the several advantages of these nanocarriers some ofthem pose challenges of their own For instance liposomeshave been used as a potential carrier with unique advantagesincluding protecting drugs from degradation reduction intoxicity or side effects but the applications of liposomes werefound to be limited due to the inherent problems such aslow encapsulation efficiency poor solubility of many drugsin the lipidsurfactant solution and rapid leakage of watersoluble drug in the presence of blood components as wellas unpredictable storage stability [19] Since precise tumortargeting with reduction in toxicity is the chief objective incancer therapy some nanocarriers like immunoliposomes(a class of liposomes) exhibit their inability to activelytarget the specific cells because the ligands conjugatedwith liposomes may increase the liposome size and reduceextravasation which may tend to be rapidly cleared by thecells of reticuloendothelial system (RES) [20] Similarlytargeted nanoparticles (NPs) also facedmany challenges Onechallenge faced by targeting NPs is that NPs might changethe stability solubility and pharmacokinetic properties ofthe carried drugs while another challenge is associated withthe shelf life aggregation leakage and toxicity of materials

used to make NPs for example poly (lactic-co-glycolicacid) (PLGA) a polymer of choice nowadays among theresearchers to fabricate NPs because of their low toxicity andhigh targeting efficiency but they degrade quickly and donot circulate in tissues long enough for sustained druggenedelivery which limits their usability in long term cancertherapy On the other hand CNTs can persist in the bodyfor weeks months or even years thus limiting their use forrepeated treatments [15 21] If we talk about dendrimers theyare synthetic branched macromolecules that form a treelikestructure whose synthesis represents a relatively new field inpolymer chemistryThough promising dendrimers are moreexpensive than other nanocarriers like CNTs and requiremany repetitive steps for synthesis posing a challenge forlarge-scale production [22] In the recent years of researchreported data clearly reveals that CNTs have an enormouspotential and possess high entrapment efficiency to carrythe therapeutic molecule as earliest to the site of cancer cellwithout activating the immune system and damage to otherviable cells although toxicity issues related to CNTs are underresearch This review highlights the insights of the CNTs andtheir potency in delivering the anticancer drugs to combatvarious metastatic cancer cells specifically

2 Production of CNTs

The production of CNTs complies with the transformation ofa carbon source into nanotubes usually at high temperatureand low pressure wherein the synthesis conditions influencethe characteristics of the final product Since prepared CNTsare usually associated with carbonaceous or metallic impu-rities therefore purification is an essential step to be con-sidered [23] Methods of CNTs purification include chemicalmethods particularly oxidation (gas phase [24] liquid phase[25]) physical methods (filtration [26] centrifugation [27]and high temperature annealing [28] etc) and multisteppurification [29]


Powersource

(+)

C deposit

Pump Gas



(a)

CnHn

Substrate

gasCarrierOutlet

coilsHeatingchamber

Reaction


depositsCarbon

(b)

chamberReaction


depositsCarbon

Nd-yaglaser

Graphitetarget

Furnace

(c)












CNTs on the cathode

Gaseousenvironment

(a)


temperature




(b)


Directed on




(c)











2








2laser operating








3 Functionalization





(a)

(b)

(c)(d)

(e)

(f)

(g)(h)

TO

OC

G

C

G

O

O

PO O

A

OO O P

O

OO

O

O

O

HN

OH

NNN NHNH

O O

Glu

3

O

O

O

O

OH

O

n

COOH

COOH

COOH

COOH

COOH

HOOC

HOOC

NO

O

NH

BAm

NH

OO

NH

FITC

O

HN

O

CONH2

OO

O

O O

SNH

NH

N SiH

H

H

HN

HN

O

O FeFe

FeO

OC

HN

O

HN

NH

NHO

NH

O

NH



2SO4or concHNO

3) which








2SO4and HNO









(1)

(2)(4)

(5)

(6)

(3)

(7)(8)

(9)(10)

(11)

(a)

(b)

(c)



with ligand


coated pits


Receptor recycling

Endosomes

Nucleus

















ble1Im

pactof

functio

nalized

CNTs

oncancer

celllin

es

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Brain

cancer

MWCN

Tsmdash

mdash

Influ

ence

ofpu

rityand

surfa

ceoxidationon

cytotoxicityof

MWCN

Tswith

human

neurob

lasto

ma

cells

Hum

anneurob

lasto

mac

ell

lineS

H-SY5

Y

With

prolon

gedcultu

reslossof

cell

viabilitywas

minim

alforp

reparatio

nswith

99pu

ritybu

tsignificantadverse

effectswered

etectedwith

97pu

rityand

with

acid

treated

preparationsA

concentrationof

5ndash10120583gmLof

MWCN

Tsseem

sidealforg

enea

nddrug


[115]

SWCN

Ts

Phosph

olipid-polyethylene

glycol(PEG

)proteinA

fluorescein

labeledintegrin

120572v1205733mAb

mdash

Functio

nalSWCN

Tsbased

onan


forthe

high

lyeffi

cient

cancer

line

Hum

anU-87M

Gglioblastomac

ell

MCF

-7

Invitro

study

revealed

that

SWCN

T-PE

G-m

Abpresentedah

igh

targetingeffi

ciency

onintegrin

120572v1205733-positive

U87MGcells

with

low

cellu

lartoxicity

[116]

MWCN

TsAng

iopep-2PE

Gylated

Doxorub

icin

Targeted

deliveryof

antic

ancerd

rugs

tobrain

gliomab

yPE

Gylated

oxidized

MWCN

Tsmod

ified

with

angiop

ep-2

C6gliomac

ells

Ang

iopep-2mod

ified

PEGylated

MWCN

Tsshow

edbette

rantiglio

ma

activ

itygoo

dcompatib

ilityand

low

toxicity

[117]

MWCN

TsPo

ly(acrylicacid)a

ndfolic

acid

Doxorub

icin


doxorubicinto

cancer

cells


magnetic

MWCN

Ts

U87

human

glioblastomac

ells

Dualtargetin

gof

doxorubicinfro

mmagnetic

MWCN

Tsshow

edenhanced


human

glioblastomac

ellscomparedwith

free

doxorubicin

[118]

SWCN

TsCD

133mon

oclonal

antib

ody(m

AB)

mdash

Phototherm

olysisof

glioblastomas

tem

likec

ells

targeted

byCN

Tconjug

ated

with

CD133

mAB

GBM

-CD133+

and

GBM

-CD133minus

cells

GBM

-CD133+

cells

weres

electiv

elytargeted

anderadicated

whereas

CD133minus

cells

remainedviableaft

erincubatio

nwith

SWCN

T-CD

133m

AB

GBM

-CD133+

cells

pretreated

with

SWCN

T-CD

133m

ABandirr

adiatedby

near-in

frared

laserfor

2days

didno


cancer

stem

like

cells

features

fortum

orgrow

th

[119]

MWCN

Tsmdash

SiRN

Aand

DNA

Internalizationof

MWCN

Tsby

microglia


immun

otherapy

ofbrain

tumors

BV2microgliaand

GL261

gliomac

ells

Uptakeo

fMWCN

Tsby

both

BV2and

GL2

61cells

invitro

with

outany

significantsigns

ofcytotoxicity

[120]

Bloo

dcancer

SWCN

TsSgc8ca

ptam

erDauno

rubicin

(Dau)


controlledreleased

elivery

ofdaun

orub

icin

tocancer

cells

byaptamer-w

rapp

edCN

Ts

Hum

anTcell

leuk

emiacell

MOLT

-4andU266

myelomac

ells

Thetertia

rycomplex

Dau-aptam

er-SWCN

Tswas

internalized

effectiv

elyto

MOLT

-4cells

butn

otto

U266cells


comparedto

Dau-aptam

er-SWCN

Tscomplex

isableto

selectively

target

MOLT

-4cells

[121]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo


thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn


CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell


Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


Powersource

(+)

C deposit

Pump Gas



(a)

CnHn

Substrate

gasCarrierOutlet

coilsHeatingchamber

Reaction


depositsCarbon

(b)

chamberReaction


depositsCarbon

Nd-yaglaser

Graphitetarget

Furnace

(c)












CNTs on the cathode

Gaseousenvironment

(a)


temperature




(b)


Directed on




(c)











2








2laser operating








3 Functionalization





(a)

(b)

(c)(d)

(e)

(f)

(g)(h)

TO

OC

G

C

G

O

O

PO O

A

OO O P

O

OO

O

O

O

HN

OH

NNN NHNH

O O

Glu

3

O

O

O

O

OH

O

n

COOH

COOH

COOH

COOH

COOH

HOOC

HOOC

NO

O

NH

BAm

NH

OO

NH

FITC

O

HN

O

CONH2

OO

O

O O

SNH

NH

N SiH

H

H

HN

HN

O

O FeFe

FeO

OC

HN

O

HN

NH

NHO

NH

O

NH



2SO4or concHNO

3) which








2SO4and HNO









(1)

(2)(4)

(5)

(6)

(3)

(7)(8)

(9)(10)

(11)

(a)

(b)

(c)



with ligand


coated pits


Receptor recycling

Endosomes

Nucleus

















ble1Im

pactof

functio

nalized

CNTs

oncancer

celllin

es

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Brain

cancer

MWCN

Tsmdash

mdash

Influ

ence

ofpu

rityand

surfa

ceoxidationon

cytotoxicityof

MWCN

Tswith

human

neurob

lasto

ma

cells

Hum

anneurob

lasto

mac

ell

lineS

H-SY5

Y

With

prolon

gedcultu

reslossof

cell

viabilitywas

minim

alforp

reparatio

nswith

99pu

ritybu

tsignificantadverse

effectswered

etectedwith

97pu

rityand

with

acid

treated

preparationsA

concentrationof

5ndash10120583gmLof

MWCN

Tsseem

sidealforg

enea

nddrug


[115]

SWCN

Ts

Phosph

olipid-polyethylene

glycol(PEG

)proteinA

fluorescein

labeledintegrin

120572v1205733mAb

mdash

Functio

nalSWCN

Tsbased

onan


forthe

high

lyeffi

cient

cancer

line

Hum

anU-87M

Gglioblastomac

ell

MCF

-7

Invitro

study

revealed

that

SWCN

T-PE

G-m

Abpresentedah

igh

targetingeffi

ciency

onintegrin

120572v1205733-positive

U87MGcells

with

low

cellu

lartoxicity

[116]

MWCN

TsAng

iopep-2PE

Gylated

Doxorub

icin

Targeted

deliveryof

antic

ancerd

rugs

tobrain

gliomab

yPE

Gylated

oxidized

MWCN

Tsmod

ified

with

angiop

ep-2

C6gliomac

ells

Ang

iopep-2mod

ified

PEGylated

MWCN

Tsshow

edbette

rantiglio

ma

activ

itygoo

dcompatib

ilityand

low

toxicity

[117]

MWCN

TsPo

ly(acrylicacid)a

ndfolic

acid

Doxorub

icin


doxorubicinto

cancer

cells


magnetic

MWCN

Ts

U87

human

glioblastomac

ells

Dualtargetin

gof

doxorubicinfro

mmagnetic

MWCN

Tsshow

edenhanced


human

glioblastomac

ellscomparedwith

free

doxorubicin

[118]

SWCN

TsCD

133mon

oclonal

antib

ody(m

AB)

mdash

Phototherm

olysisof

glioblastomas

tem

likec

ells

targeted

byCN

Tconjug

ated

with

CD133

mAB

GBM

-CD133+

and

GBM

-CD133minus

cells

GBM

-CD133+

cells

weres

electiv

elytargeted

anderadicated

whereas

CD133minus

cells

remainedviableaft

erincubatio

nwith

SWCN

T-CD

133m

AB

GBM

-CD133+

cells

pretreated

with

SWCN

T-CD

133m

ABandirr

adiatedby

near-in

frared

laserfor

2days

didno


cancer

stem

like

cells

features

fortum

orgrow

th

[119]

MWCN

Tsmdash

SiRN

Aand

DNA

Internalizationof

MWCN

Tsby

microglia


immun

otherapy

ofbrain

tumors

BV2microgliaand

GL261

gliomac

ells

Uptakeo

fMWCN

Tsby

both

BV2and

GL2

61cells

invitro

with

outany

significantsigns

ofcytotoxicity

[120]

Bloo

dcancer

SWCN

TsSgc8ca

ptam

erDauno

rubicin

(Dau)


controlledreleased

elivery

ofdaun

orub

icin

tocancer

cells

byaptamer-w

rapp

edCN

Ts

Hum

anTcell

leuk

emiacell

MOLT

-4andU266

myelomac

ells

Thetertia

rycomplex

Dau-aptam

er-SWCN

Tswas

internalized

effectiv

elyto

MOLT

-4cells

butn

otto

U266cells


comparedto

Dau-aptam

er-SWCN

Tscomplex

isableto

selectively

target

MOLT

-4cells

[121]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo


thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn


CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell


Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of






CNTs on the cathode

Gaseousenvironment

(a)


temperature




(b)


Directed on




(c)











2








2laser operating








3 Functionalization





(a)

(b)

(c)(d)

(e)

(f)

(g)(h)

TO

OC

G

C

G

O

O

PO O

A

OO O P

O

OO

O

O

O

HN

OH

NNN NHNH

O O

Glu

3

O

O

O

O

OH

O

n

COOH

COOH

COOH

COOH

COOH

HOOC

HOOC

NO

O

NH

BAm

NH

OO

NH

FITC

O

HN

O

CONH2

OO

O

O O

SNH

NH

N SiH

H

H

HN

HN

O

O FeFe

FeO

OC

HN

O

HN

NH

NHO

NH

O

NH



2SO4or concHNO

3) which








2SO4and HNO









(1)

(2)(4)

(5)

(6)

(3)

(7)(8)

(9)(10)

(11)

(a)

(b)

(c)



with ligand


coated pits


Receptor recycling

Endosomes

Nucleus

















ble1Im

pactof

functio

nalized

CNTs

oncancer

celllin

es

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Brain

cancer

MWCN

Tsmdash

mdash

Influ

ence

ofpu

rityand

surfa

ceoxidationon

cytotoxicityof

MWCN

Tswith

human

neurob

lasto

ma

cells

Hum

anneurob

lasto

mac

ell

lineS

H-SY5

Y

With

prolon

gedcultu

reslossof

cell

viabilitywas

minim

alforp

reparatio

nswith

99pu

ritybu

tsignificantadverse

effectswered

etectedwith

97pu

rityand

with

acid

treated

preparationsA

concentrationof

5ndash10120583gmLof

MWCN

Tsseem

sidealforg

enea

nddrug


[115]

SWCN

Ts

Phosph

olipid-polyethylene

glycol(PEG

)proteinA

fluorescein

labeledintegrin

120572v1205733mAb

mdash

Functio

nalSWCN

Tsbased

onan


forthe

high

lyeffi

cient

cancer

line

Hum

anU-87M

Gglioblastomac

ell

MCF

-7

Invitro

study

revealed

that

SWCN

T-PE

G-m

Abpresentedah

igh

targetingeffi

ciency

onintegrin

120572v1205733-positive

U87MGcells

with

low

cellu

lartoxicity

[116]

MWCN

TsAng

iopep-2PE

Gylated

Doxorub

icin

Targeted

deliveryof

antic

ancerd

rugs

tobrain

gliomab

yPE

Gylated

oxidized

MWCN

Tsmod

ified

with

angiop

ep-2

C6gliomac

ells

Ang

iopep-2mod

ified

PEGylated

MWCN

Tsshow

edbette

rantiglio

ma

activ

itygoo

dcompatib

ilityand

low

toxicity

[117]

MWCN

TsPo

ly(acrylicacid)a

ndfolic

acid

Doxorub

icin


doxorubicinto

cancer

cells


magnetic

MWCN

Ts

U87

human

glioblastomac

ells

Dualtargetin

gof

doxorubicinfro

mmagnetic

MWCN

Tsshow

edenhanced


human

glioblastomac

ellscomparedwith

free

doxorubicin

[118]

SWCN

TsCD

133mon

oclonal

antib

ody(m

AB)

mdash

Phototherm

olysisof

glioblastomas

tem

likec

ells

targeted

byCN

Tconjug

ated

with

CD133

mAB

GBM

-CD133+

and

GBM

-CD133minus

cells

GBM

-CD133+

cells

weres

electiv

elytargeted

anderadicated

whereas

CD133minus

cells

remainedviableaft

erincubatio

nwith

SWCN

T-CD

133m

AB

GBM

-CD133+

cells

pretreated

with

SWCN

T-CD

133m

ABandirr

adiatedby

near-in

frared

laserfor

2days

didno


cancer

stem

like

cells

features

fortum

orgrow

th

[119]

MWCN

Tsmdash

SiRN

Aand

DNA

Internalizationof

MWCN

Tsby

microglia


immun

otherapy

ofbrain

tumors

BV2microgliaand

GL261

gliomac

ells

Uptakeo

fMWCN

Tsby

both

BV2and

GL2

61cells

invitro

with

outany

significantsigns

ofcytotoxicity

[120]

Bloo

dcancer

SWCN

TsSgc8ca

ptam

erDauno

rubicin

(Dau)


controlledreleased

elivery

ofdaun

orub

icin

tocancer

cells

byaptamer-w

rapp

edCN

Ts

Hum

anTcell

leuk

emiacell

MOLT

-4andU266

myelomac

ells

Thetertia

rycomplex

Dau-aptam

er-SWCN

Tswas

internalized

effectiv

elyto

MOLT

-4cells

butn

otto

U266cells


comparedto

Dau-aptam

er-SWCN

Tscomplex

isableto

selectively

target

MOLT

-4cells

[121]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo


thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn


CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell


Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of






2laser operating








3 Functionalization





(a)

(b)

(c)(d)

(e)

(f)

(g)(h)

TO

OC

G

C

G

O

O

PO O

A

OO O P

O

OO

O

O

O

HN

OH

NNN NHNH

O O

Glu

3

O

O

O

O

OH

O

n

COOH

COOH

COOH

COOH

COOH

HOOC

HOOC

NO

O

NH

BAm

NH

OO

NH

FITC

O

HN

O

CONH2

OO

O

O O

SNH

NH

N SiH

H

H

HN

HN

O

O FeFe

FeO

OC

HN

O

HN

NH

NHO

NH

O

NH



2SO4or concHNO

3) which








2SO4and HNO









(1)

(2)(4)

(5)

(6)

(3)

(7)(8)

(9)(10)

(11)

(a)

(b)

(c)



with ligand


coated pits


Receptor recycling

Endosomes

Nucleus

















ble1Im

pactof

functio

nalized

CNTs

oncancer

celllin

es

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Brain

cancer

MWCN

Tsmdash

mdash

Influ

ence

ofpu

rityand

surfa

ceoxidationon

cytotoxicityof

MWCN

Tswith

human

neurob

lasto

ma

cells

Hum

anneurob

lasto

mac

ell

lineS

H-SY5

Y

With

prolon

gedcultu

reslossof

cell

viabilitywas

minim

alforp

reparatio

nswith

99pu

ritybu

tsignificantadverse

effectswered

etectedwith

97pu

rityand

with

acid

treated

preparationsA

concentrationof

5ndash10120583gmLof

MWCN

Tsseem

sidealforg

enea

nddrug


[115]

SWCN

Ts

Phosph

olipid-polyethylene

glycol(PEG

)proteinA

fluorescein

labeledintegrin

120572v1205733mAb

mdash

Functio

nalSWCN

Tsbased

onan


forthe

high

lyeffi

cient

cancer

line

Hum

anU-87M

Gglioblastomac

ell

MCF

-7

Invitro

study

revealed

that

SWCN

T-PE

G-m

Abpresentedah

igh

targetingeffi

ciency

onintegrin

120572v1205733-positive

U87MGcells

with

low

cellu

lartoxicity

[116]

MWCN

TsAng

iopep-2PE

Gylated

Doxorub

icin

Targeted

deliveryof

antic

ancerd

rugs

tobrain

gliomab

yPE

Gylated

oxidized

MWCN

Tsmod

ified

with

angiop

ep-2

C6gliomac

ells

Ang

iopep-2mod

ified

PEGylated

MWCN

Tsshow

edbette

rantiglio

ma

activ

itygoo

dcompatib

ilityand

low

toxicity

[117]

MWCN

TsPo

ly(acrylicacid)a

ndfolic

acid

Doxorub

icin


doxorubicinto

cancer

cells


magnetic

MWCN

Ts

U87

human

glioblastomac

ells

Dualtargetin

gof

doxorubicinfro

mmagnetic

MWCN

Tsshow

edenhanced


human

glioblastomac

ellscomparedwith

free

doxorubicin

[118]

SWCN

TsCD

133mon

oclonal

antib

ody(m

AB)

mdash

Phototherm

olysisof

glioblastomas

tem

likec

ells

targeted

byCN

Tconjug

ated

with

CD133

mAB

GBM

-CD133+

and

GBM

-CD133minus

cells

GBM

-CD133+

cells

weres

electiv

elytargeted

anderadicated

whereas

CD133minus

cells

remainedviableaft

erincubatio

nwith

SWCN

T-CD

133m

AB

GBM

-CD133+

cells

pretreated

with

SWCN

T-CD

133m

ABandirr

adiatedby

near-in

frared

laserfor

2days

didno


cancer

stem

like

cells

features

fortum

orgrow

th

[119]

MWCN

Tsmdash

SiRN

Aand

DNA

Internalizationof

MWCN

Tsby

microglia


immun

otherapy

ofbrain

tumors

BV2microgliaand

GL261

gliomac

ells

Uptakeo

fMWCN

Tsby

both

BV2and

GL2

61cells

invitro

with

outany

significantsigns

ofcytotoxicity

[120]

Bloo

dcancer

SWCN

TsSgc8ca

ptam

erDauno

rubicin

(Dau)


controlledreleased

elivery

ofdaun

orub

icin

tocancer

cells

byaptamer-w

rapp

edCN

Ts

Hum

anTcell

leuk

emiacell

MOLT

-4andU266

myelomac

ells

Thetertia

rycomplex

Dau-aptam

er-SWCN

Tswas

internalized

effectiv

elyto

MOLT

-4cells

butn

otto

U266cells


comparedto

Dau-aptam

er-SWCN

Tscomplex

isableto

selectively

target

MOLT

-4cells

[121]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo


thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn


CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell


Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


(a)

(b)

(c)(d)

(e)

(f)

(g)(h)

TO

OC

G

C

G

O

O

PO O

A

OO O P

O

OO

O

O

O

HN

OH

NNN NHNH

O O

Glu

3

O

O

O

O

OH

O

n

COOH

COOH

COOH

COOH

COOH

HOOC

HOOC

NO

O

NH

BAm

NH

OO

NH

FITC

O

HN

O

CONH2

OO

O

O O

SNH

NH

N SiH

H

H

HN

HN

O

O FeFe

FeO

OC

HN

O

HN

NH

NHO

NH

O

NH



2SO4or concHNO

3) which








2SO4and HNO









(1)

(2)(4)

(5)

(6)

(3)

(7)(8)

(9)(10)

(11)

(a)

(b)

(c)



with ligand


coated pits


Receptor recycling

Endosomes

Nucleus

















ble1Im

pactof

functio

nalized

CNTs

oncancer

celllin

es

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Brain

cancer

MWCN

Tsmdash

mdash

Influ

ence

ofpu

rityand

surfa

ceoxidationon

cytotoxicityof

MWCN

Tswith

human

neurob

lasto

ma

cells

Hum

anneurob

lasto

mac

ell

lineS

H-SY5

Y

With

prolon

gedcultu

reslossof

cell

viabilitywas

minim

alforp

reparatio

nswith

99pu

ritybu

tsignificantadverse

effectswered

etectedwith

97pu

rityand

with

acid

treated

preparationsA

concentrationof

5ndash10120583gmLof

MWCN

Tsseem

sidealforg

enea

nddrug


[115]

SWCN

Ts

Phosph

olipid-polyethylene

glycol(PEG

)proteinA

fluorescein

labeledintegrin

120572v1205733mAb

mdash

Functio

nalSWCN

Tsbased

onan


forthe

high

lyeffi

cient

cancer

line

Hum

anU-87M

Gglioblastomac

ell

MCF

-7

Invitro

study

revealed

that

SWCN

T-PE

G-m

Abpresentedah

igh

targetingeffi

ciency

onintegrin

120572v1205733-positive

U87MGcells

with

low

cellu

lartoxicity

[116]

MWCN

TsAng

iopep-2PE

Gylated

Doxorub

icin

Targeted

deliveryof

antic

ancerd

rugs

tobrain

gliomab

yPE

Gylated

oxidized

MWCN

Tsmod

ified

with

angiop

ep-2

C6gliomac

ells

Ang

iopep-2mod

ified

PEGylated

MWCN

Tsshow

edbette

rantiglio

ma

activ

itygoo

dcompatib

ilityand

low

toxicity

[117]

MWCN

TsPo

ly(acrylicacid)a

ndfolic

acid

Doxorub

icin


doxorubicinto

cancer

cells


magnetic

MWCN

Ts

U87

human

glioblastomac

ells

Dualtargetin

gof

doxorubicinfro

mmagnetic

MWCN

Tsshow

edenhanced


human

glioblastomac

ellscomparedwith

free

doxorubicin

[118]

SWCN

TsCD

133mon

oclonal

antib

ody(m

AB)

mdash

Phototherm

olysisof

glioblastomas

tem

likec

ells

targeted

byCN

Tconjug

ated

with

CD133

mAB

GBM

-CD133+

and

GBM

-CD133minus

cells

GBM

-CD133+

cells

weres

electiv

elytargeted

anderadicated

whereas

CD133minus

cells

remainedviableaft

erincubatio

nwith

SWCN

T-CD

133m

AB

GBM

-CD133+

cells

pretreated

with

SWCN

T-CD

133m

ABandirr

adiatedby

near-in

frared

laserfor

2days

didno


cancer

stem

like

cells

features

fortum

orgrow

th

[119]

MWCN

Tsmdash

SiRN

Aand

DNA

Internalizationof

MWCN

Tsby

microglia


immun

otherapy

ofbrain

tumors

BV2microgliaand

GL261

gliomac

ells

Uptakeo

fMWCN

Tsby

both

BV2and

GL2

61cells

invitro

with

outany

significantsigns

ofcytotoxicity

[120]

Bloo

dcancer

SWCN

TsSgc8ca

ptam

erDauno

rubicin

(Dau)


controlledreleased

elivery

ofdaun

orub

icin

tocancer

cells

byaptamer-w

rapp

edCN

Ts

Hum

anTcell

leuk

emiacell

MOLT

-4andU266

myelomac

ells

Thetertia

rycomplex

Dau-aptam

er-SWCN

Tswas

internalized

effectiv

elyto

MOLT

-4cells

butn

otto

U266cells


comparedto

Dau-aptam

er-SWCN

Tscomplex

isableto

selectively

target

MOLT

-4cells

[121]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo


thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn


CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell


Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




2SO4and HNO









(1)

(2)(4)

(5)

(6)

(3)

(7)(8)

(9)(10)

(11)

(a)

(b)

(c)



with ligand


coated pits


Receptor recycling

Endosomes

Nucleus

















ble1Im

pactof

functio

nalized

CNTs

oncancer

celllin

es

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Brain

cancer

MWCN

Tsmdash

mdash

Influ

ence

ofpu

rityand

surfa

ceoxidationon

cytotoxicityof

MWCN

Tswith

human

neurob

lasto

ma

cells

Hum

anneurob

lasto

mac

ell

lineS

H-SY5

Y

With

prolon

gedcultu

reslossof

cell

viabilitywas

minim

alforp

reparatio

nswith

99pu

ritybu

tsignificantadverse

effectswered

etectedwith

97pu

rityand

with

acid

treated

preparationsA

concentrationof

5ndash10120583gmLof

MWCN

Tsseem

sidealforg

enea

nddrug


[115]

SWCN

Ts

Phosph

olipid-polyethylene

glycol(PEG

)proteinA

fluorescein

labeledintegrin

120572v1205733mAb

mdash

Functio

nalSWCN

Tsbased

onan


forthe

high

lyeffi

cient

cancer

line

Hum

anU-87M

Gglioblastomac

ell

MCF

-7

Invitro

study

revealed

that

SWCN

T-PE

G-m

Abpresentedah

igh

targetingeffi

ciency

onintegrin

120572v1205733-positive

U87MGcells

with

low

cellu

lartoxicity

[116]

MWCN

TsAng

iopep-2PE

Gylated

Doxorub

icin

Targeted

deliveryof

antic

ancerd

rugs

tobrain

gliomab

yPE

Gylated

oxidized

MWCN

Tsmod

ified

with

angiop

ep-2

C6gliomac

ells

Ang

iopep-2mod

ified

PEGylated

MWCN

Tsshow

edbette

rantiglio

ma

activ

itygoo

dcompatib

ilityand

low

toxicity

[117]

MWCN

TsPo

ly(acrylicacid)a

ndfolic

acid

Doxorub

icin


doxorubicinto

cancer

cells


magnetic

MWCN

Ts

U87

human

glioblastomac

ells

Dualtargetin

gof

doxorubicinfro

mmagnetic

MWCN

Tsshow

edenhanced


human

glioblastomac

ellscomparedwith

free

doxorubicin

[118]

SWCN

TsCD

133mon

oclonal

antib

ody(m

AB)

mdash

Phototherm

olysisof

glioblastomas

tem

likec

ells

targeted

byCN

Tconjug

ated

with

CD133

mAB

GBM

-CD133+

and

GBM

-CD133minus

cells

GBM

-CD133+

cells

weres

electiv

elytargeted

anderadicated

whereas

CD133minus

cells

remainedviableaft

erincubatio

nwith

SWCN

T-CD

133m

AB

GBM

-CD133+

cells

pretreated

with

SWCN

T-CD

133m

ABandirr

adiatedby

near-in

frared

laserfor

2days

didno


cancer

stem

like

cells

features

fortum

orgrow

th

[119]

MWCN

Tsmdash

SiRN

Aand

DNA

Internalizationof

MWCN

Tsby

microglia


immun

otherapy

ofbrain

tumors

BV2microgliaand

GL261

gliomac

ells

Uptakeo

fMWCN

Tsby

both

BV2and

GL2

61cells

invitro

with

outany

significantsigns

ofcytotoxicity

[120]

Bloo

dcancer

SWCN

TsSgc8ca

ptam

erDauno

rubicin

(Dau)


controlledreleased

elivery

ofdaun

orub

icin

tocancer

cells

byaptamer-w

rapp

edCN

Ts

Hum

anTcell

leuk

emiacell

MOLT

-4andU266

myelomac

ells

Thetertia

rycomplex

Dau-aptam

er-SWCN

Tswas

internalized

effectiv

elyto

MOLT

-4cells

butn

otto

U266cells


comparedto

Dau-aptam

er-SWCN

Tscomplex

isableto

selectively

target

MOLT

-4cells

[121]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo


thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn


CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell


Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


(1)

(2)(4)

(5)

(6)

(3)

(7)(8)

(9)(10)

(11)

(a)

(b)

(c)



with ligand


coated pits


Receptor recycling

Endosomes

Nucleus

















ble1Im

pactof

functio

nalized

CNTs

oncancer

celllin

es

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Brain

cancer

MWCN

Tsmdash

mdash

Influ

ence

ofpu

rityand

surfa

ceoxidationon

cytotoxicityof

MWCN

Tswith

human

neurob

lasto

ma

cells

Hum

anneurob

lasto

mac

ell

lineS

H-SY5

Y

With

prolon

gedcultu

reslossof

cell

viabilitywas

minim

alforp

reparatio

nswith

99pu

ritybu

tsignificantadverse

effectswered

etectedwith

97pu

rityand

with

acid

treated

preparationsA

concentrationof

5ndash10120583gmLof

MWCN

Tsseem

sidealforg

enea

nddrug


[115]

SWCN

Ts

Phosph

olipid-polyethylene

glycol(PEG

)proteinA

fluorescein

labeledintegrin

120572v1205733mAb

mdash

Functio

nalSWCN

Tsbased

onan


forthe

high

lyeffi

cient

cancer

line

Hum

anU-87M

Gglioblastomac

ell

MCF

-7

Invitro

study

revealed

that

SWCN

T-PE

G-m

Abpresentedah

igh

targetingeffi

ciency

onintegrin

120572v1205733-positive

U87MGcells

with

low

cellu

lartoxicity

[116]

MWCN

TsAng

iopep-2PE

Gylated

Doxorub

icin

Targeted

deliveryof

antic

ancerd

rugs

tobrain

gliomab

yPE

Gylated

oxidized

MWCN

Tsmod

ified

with

angiop

ep-2

C6gliomac

ells

Ang

iopep-2mod

ified

PEGylated

MWCN

Tsshow

edbette

rantiglio

ma

activ

itygoo

dcompatib

ilityand

low

toxicity

[117]

MWCN

TsPo

ly(acrylicacid)a

ndfolic

acid

Doxorub

icin


doxorubicinto

cancer

cells


magnetic

MWCN

Ts

U87

human

glioblastomac

ells

Dualtargetin

gof

doxorubicinfro

mmagnetic

MWCN

Tsshow

edenhanced


human

glioblastomac

ellscomparedwith

free

doxorubicin

[118]

SWCN

TsCD

133mon

oclonal

antib

ody(m

AB)

mdash

Phototherm

olysisof

glioblastomas

tem

likec

ells

targeted

byCN

Tconjug

ated

with

CD133

mAB

GBM

-CD133+

and

GBM

-CD133minus

cells

GBM

-CD133+

cells

weres

electiv

elytargeted

anderadicated

whereas

CD133minus

cells

remainedviableaft

erincubatio

nwith

SWCN

T-CD

133m

AB

GBM

-CD133+

cells

pretreated

with

SWCN

T-CD

133m

ABandirr

adiatedby

near-in

frared

laserfor

2days

didno


cancer

stem

like

cells

features

fortum

orgrow

th

[119]

MWCN

Tsmdash

SiRN

Aand

DNA

Internalizationof

MWCN

Tsby

microglia


immun

otherapy

ofbrain

tumors

BV2microgliaand

GL261

gliomac

ells

Uptakeo

fMWCN

Tsby

both

BV2and

GL2

61cells

invitro

with

outany

significantsigns

ofcytotoxicity

[120]

Bloo

dcancer

SWCN

TsSgc8ca

ptam

erDauno

rubicin

(Dau)


controlledreleased

elivery

ofdaun

orub

icin

tocancer

cells

byaptamer-w

rapp

edCN

Ts

Hum

anTcell

leuk

emiacell

MOLT

-4andU266

myelomac

ells

Thetertia

rycomplex

Dau-aptam

er-SWCN

Tswas

internalized

effectiv

elyto

MOLT

-4cells

butn

otto

U266cells


comparedto

Dau-aptam

er-SWCN

Tscomplex

isableto

selectively

target

MOLT

-4cells

[121]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo


thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn


CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell


Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of













ble1Im

pactof

functio

nalized

CNTs

oncancer

celllin

es

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Brain

cancer

MWCN

Tsmdash

mdash

Influ

ence

ofpu

rityand

surfa

ceoxidationon

cytotoxicityof

MWCN

Tswith

human

neurob

lasto

ma

cells

Hum

anneurob

lasto

mac

ell

lineS

H-SY5

Y

With

prolon

gedcultu

reslossof

cell

viabilitywas

minim

alforp

reparatio

nswith

99pu

ritybu

tsignificantadverse

effectswered

etectedwith

97pu

rityand

with

acid

treated

preparationsA

concentrationof

5ndash10120583gmLof

MWCN

Tsseem

sidealforg

enea

nddrug


[115]

SWCN

Ts

Phosph

olipid-polyethylene

glycol(PEG

)proteinA

fluorescein

labeledintegrin

120572v1205733mAb

mdash

Functio

nalSWCN

Tsbased

onan


forthe

high

lyeffi

cient

cancer

line

Hum

anU-87M

Gglioblastomac

ell

MCF

-7

Invitro

study

revealed

that

SWCN

T-PE

G-m

Abpresentedah

igh

targetingeffi

ciency

onintegrin

120572v1205733-positive

U87MGcells

with

low

cellu

lartoxicity

[116]

MWCN

TsAng

iopep-2PE

Gylated

Doxorub

icin

Targeted

deliveryof

antic

ancerd

rugs

tobrain

gliomab

yPE

Gylated

oxidized

MWCN

Tsmod

ified

with

angiop

ep-2

C6gliomac

ells

Ang

iopep-2mod

ified

PEGylated

MWCN

Tsshow

edbette

rantiglio

ma

activ

itygoo

dcompatib

ilityand

low

toxicity

[117]

MWCN

TsPo

ly(acrylicacid)a

ndfolic

acid

Doxorub

icin


doxorubicinto

cancer

cells


magnetic

MWCN

Ts

U87

human

glioblastomac

ells

Dualtargetin

gof

doxorubicinfro

mmagnetic

MWCN

Tsshow

edenhanced


human

glioblastomac

ellscomparedwith

free

doxorubicin

[118]

SWCN

TsCD

133mon

oclonal

antib

ody(m

AB)

mdash

Phototherm

olysisof

glioblastomas

tem

likec

ells

targeted

byCN

Tconjug

ated

with

CD133

mAB

GBM

-CD133+

and

GBM

-CD133minus

cells

GBM

-CD133+

cells

weres

electiv

elytargeted

anderadicated

whereas

CD133minus

cells

remainedviableaft

erincubatio

nwith

SWCN

T-CD

133m

AB

GBM

-CD133+

cells

pretreated

with

SWCN

T-CD

133m

ABandirr

adiatedby

near-in

frared

laserfor

2days

didno


cancer

stem

like

cells

features

fortum

orgrow

th

[119]

MWCN

Tsmdash

SiRN

Aand

DNA

Internalizationof

MWCN

Tsby

microglia


immun

otherapy

ofbrain

tumors

BV2microgliaand

GL261

gliomac

ells

Uptakeo

fMWCN

Tsby

both

BV2and

GL2

61cells

invitro

with

outany

significantsigns

ofcytotoxicity

[120]

Bloo

dcancer

SWCN

TsSgc8ca

ptam

erDauno

rubicin

(Dau)


controlledreleased

elivery

ofdaun

orub

icin

tocancer

cells

byaptamer-w

rapp

edCN

Ts

Hum

anTcell

leuk

emiacell

MOLT

-4andU266

myelomac

ells

Thetertia

rycomplex

Dau-aptam

er-SWCN

Tswas

internalized

effectiv

elyto

MOLT

-4cells

butn

otto

U266cells


comparedto

Dau-aptam

er-SWCN

Tscomplex

isableto

selectively

target

MOLT

-4cells

[121]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo


thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn


CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell


Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Breast

cancer

SWCN

Ts

Polyethylene

glycol(PEG

)andPo

ly(m

aleic

anhydride-alt-1-

octadecene)

(PMHC 1

8)

mdash

Optim

izationof

surfa

cechem

istry

onsin

glew

alled

CNTs

forinvivo

phototherm

alablatio

nof

tumors

Balbcmiceb

earin

g4T

1tum

ors

PEG-PMHC 1

8-SW

CNTs

show

edultralon

gbloo


thou

ghshow

inghigh

uptake

inthetum

ortend

toaccumulateinthes

kinderm

is

[122]

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

MCF

-7and

MDA-

MB-435h

uman

breastcancer

celllin

eliver

cancer

cell

HepG2

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

Ts

Insulin

-like

grow

thfactor

1receptor

(IGF1R-)specific

andno

nspecific

mon

oclonalantibod

ies

(mABs)

mdashBiocon

jugatedCN

Tsfor

targetingc

ancerb

iomarkers

BT-474

andMCF

-7breastcancer

cells

mAB-CN

Tas

field

effecttransistorsa

revery

prom

ising

biosensorc

andidatesto

detectcancer

cells

[124]

SWCN

Ts

Distearoylph

osph

atidy-

lethanolam

ine

(DSP

E)-PEG

-Amine

mou

sedo

ubleminute2

homolog

(MDM2)

SiRN

A

Functio

nalized

SWCN

Tsenablese

fficient

intracellulard

elivery

ofSiRN

AtargetingMDM2to

inhibitb

reastcancerc

ells

grow

th

B-Ca

p-37

breast

carcinom

acells

f-SWCN

Tsshow

edsig

nificantefficiency

incarrying

SiRN

AandSiRN

A-MDM2

complexes

inB-Cap-37cells

andcaused

inhibitio

nof

proliferatin

gcells

[125]

SWCN

Tsmdash

mdashSW

CNTnano

bombagents

fork

illingbreastcancer

cells

Hum

anBT

-474

breast

cancer

cells

SWCN

T-basedsyste

msw

erec

apableof

killing

cancer

cells

with

outcausin

gtoxicityto

thes

urroun

ding

cells

[126]

SWCN

TsPo

lyethylene

glycol

Paclitaxel

(PTX

)Drugdeliverywith

CNTs

forinvivo

cancer

treatment4T

1murineb

reast

cancer

celllin

e

SWCN

T-PT

Xaffords

high

ereffi

cacy

insupp

ressingtumor

grow

thwith

out

causingobviou

stoxiceffectsto

norm

alorgans

[110]

SWCN

Tsanti-HER

2chickenIgY

antib

ody

mdash

Anti-H

ER2IgY

antib

ody-functio

nalized

SWCN

Tsford

etectio

nand

selectived

estructio

nof

breastcancer

cells

HER

2-expressin

gSK

-BR-3cells

and

HER

2-negativ

eMCF

-7cells

Raman

signalcollected

atsin

gle-celllevel

from

thec

omplex-tr

eatedSK

-BR-3cells

was

significantly

greaterthanthatfro

mvario

uscontrolcells

HER

2IgY-SW

CNT

complex

specifically

targeted

HER

2-expressin

gSK

-BR-3cells

butn


CF-7

cells

[78]

Colon

cancer

MWCN

Tsmdash

mdash

Verticallyaligned

MWCN

Tsto

preferentia

llyentrap

high

lymetastatic

cancer

cells

SW-48cells

and

HT-29

human

colon

adenocarcino

mac

ell


Tentrap

high

ermetastatic

cancer

inlarger

fractio

nthan

lower

metastatic

gradesC

ellrig

idity

due

tofix

ationdecreasesthe

entrapment

efficiency

[127]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Colon

cancer

SWCN

TsBo

vine

serum

albu

min-antibod

yflu

orescein

Doxorub

icin

Triplefunctio

nalizationof

SWCN

Tswith

doxorubicin

amon

oclonalantibod

yand

afluo

rescentm

arkerfor

targeted

cancer

therapy

WiD

rHum

ancolon

adenocarcino

mac

ells

Thetrip

lefictio

nalized

complex

was

efficiently

takenby

cancer

cells

with

subsequent

intracellularrele

aseo

fdo

xorubicin

[128]

Liver

cancer

MWCN

TsPo

lyam

idoamine

dend

rimer(d)

FITC

-labelled

antisense

c-myc

oligon

ucleotides

(asO

DN)

Synthesis

and

characteriz

ationof

polyam

idoamine

dend

rimer

coated

MWCN

Tsandtheir

applicationin

gene

delivery

syste

ms

HEP

-G2hu

man

hepatomac

ells

Laserc

onfocalm

icroscop

yconfi

rmed

the

entryof

asODNinto

thetum

orcell

with

in15min

ofincubatio

nasODN-dMNTs

compo

sites

inhibitthe

cellgrow

thanddo

wnregulated

the

expressio

nof

thec

-myc

gene

andC-

Myc

protein

[123]

SWCN

TsCh

itosanandfolic

acid

Doxorub

icin

Targeted

DDSbasedon

chito

sanandfolic

acid

mod

ified

SWCN

Tsfor

controllableloading

rele

ase

ofantic

ancera

gent

doxorubicin

Hepatocellular

carcinom

aSM

MC-

7721

celllin

es

Thec

hitosan-folic

acid

mod

ified

SWCN

Tsno

tonlykillcancer

cells

efficientlybut

also

displaymuchlessin

vivo

toxicitythan

freed

oxorub

icin

[129]

Lymph

node

Metastatis

MWCN

TsMagnetic

Gem

citabine

(GEM

)

Magnetic

functio

nalized

CNTs

asdrug

vehicle

sfor

cancer

lymph

node

metastasis

treatment

BxPC

-3pancreatic

cancer

cells

mMWCN

Ts-G

EMhadhigh

antitum

oractiv

ityresulting

insuccessfu

lregression

andinhibitio

nof

lymph

node

metastasis

underthe

magnetic

field

[130]

Kidn

eycancer

SWCN

Tsmdash

mdashEff

ecto

fSWCN

Tson

human

HEK

293cells

Hum

ankidn

eyem

bryo

cellHEK

-293

cells

SWCN

TsinhibitH

EK293cell

proliferatio

nanddecrease

celladhesiv

eabilityin

adosea

ndtim

edependent

manner

[131]

SWCN

TsPh

enosafranine

(PS)

and

Nile

blue

(NB)

dyes

mdash

SWCN

Tsmod

ified

with

organicd

yessynthesis

characteriz

ation

and


Baby

hamste

rkidney

fibroblastcells

BHK-

21celllin

e

Cytotoxicityof

dyem

odified

SWCN

Tdisplay

edlowtoxicityin

thed

arkwhile

beinghigh

erin

thed

arkandhigh

erin

the

presence

oflight

[132]

Cervical

cancer

SWCN

Tschito

sanandfolic

acid

FITC

mdashFu

nctio

nalSWCN

Tschito

sanconjugatefor

tumor

celltargeting

Hum

ancervical

carcinom

aHeLac

ells

Con

jugatesp

rovide

newop

tions

for

targeted

drug

deliveryandtumor

cell

sensingbecauseo

fthe

combinedintrinsic

prop

ertie

sofC

NTs

andthev

ersatility

ofchito

san

[133]

MWCN

TsFo

latea

ndiro

nDoxorub

icin

Folateandiro

ndefunctio

nalized

MWCN

Tsas

dualtargeted

drug

nano

carriertocancer

cells

HeLac

ells

Thisdu

altargeted

nano

carrierh

aseffi

cientb

iologicaland

magnetic


ards

HeLac

ells

andconsidered

safeforb

iological

applications

[134]


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


Table1Con

tinued

Cancer

type

CNTprop

ertie

sBioactive

molecule

Objectiv

eCellline

Repercussio

nof

thes

tudy

Reference

Type

Functio

nalization

Cervical

cancer

SWCN

TMWCN

T

Acid-tr

eatedSW

CNTs

acid-tr

eatedMWCN

Ts

amylosew

rapp

edSW

CNTsmdash

Theinfl

uenceo

fCNT

scaffolds

onhu

man

cervical

carcinom

aHeLac

ells


esion

kinase

expressio

n

HeLac

ells

Cellscultu

redon

SWCN

Tsandon

acid-tr

eatedSW

CNTs

werefou

ndto

undergoapop

tosis

Thec

ellscultu

redon

MWCN

Tsacid-tre

ated

MWCN

Tsand

amylosew

rapp

edSW

CNTs

werefou

ndto

beviable

Thismay

bedu

etofocal

adhesio

nkinases(FA

K)expressio

nwhich

isrespon

sibleforc

ontro

lling

thec

ell

viability

[135]

SWCN

TsPo

lysaccharid

es[sod

ium

alginate(A

LG)a

ndchito

san(C

H)]

Doxorub

icin

(DOX)

Targeted

deliveryand

controlledreleaseb

ydo

xorubicinto

cancer

cells

usingmod

ified

CNTs

HeLac

ells

TheD

OXreleased

from

them

odified

nano

tubesh

asbeen

show

nto

damage

nucle

arDNAandinhibitthe

cell

proliferatio

n

[136]

Prostate

cancer

SWCN

TsPo

lyethylenimine(PE

I)

Asn-Gly-Arg

(NGR)

peptide

SiRN

A

Synergisticantic

ancere

ffect

ofRN

Aiand

phototherm

altherapymediatedby

functio

nalized

SWCN

Ts

Hum

anprostate

carcinom

a(GIV

)cell

PC-3

cells

SWCN

T-PE

I-SiRN

A-NGRindu

cessevere

apop

tosis

andsupp

resses

thep

roliferating

ofPC

-3cells

with

outany

leveloftoxicity

[137]



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of



















































2and sw-







7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




7 Conclusion





References






























































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of














































































































































































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of

review article carbon nanotubes: an emerging drug carrier ...the laser ablation and the chemical...

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