nanobiotechnology and its applications in medical diagnostics and biomedical field 1

8/7/2019 Nanobiotechnology And Its Applications In Medical Diagnostics And Biomedical Field 1

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Nanobiotechnology And Its Applications In

Medical Diagnostics And Biomedical Field.

Maninder Singh 818Mayank 820

Pranshu Abhishek 832

Sumit Gupta 847

Rajdeep Pal 8551



What is Nanobiotechnology?

Biotechnology is the application of technological

innovation as it pertains to biological and life sciences.

Nanobiotechnology incorporates biotechnology on the

nano-scale.

2



IntroductionSize Ranges of Biological

Material

• Cells: 100um – 10um

•Cell organelles (nucleus,mitochondrion): 10um –1um

• Viruses: 100nm- 50nm

• Cell material (proteins,lipids, DNA, RNA): 10nm –0.1nm

3



WHAT IS NANOTECHNOLOGY?

* 1 millimeter = 1,000 micrometers;1 micrometer = 1,000 nanometersSource: "Nanotech: The Tiny Revolution" by CMPCientífica (November 2001)

Structures(e.g. materials)

Devices(e.g. sensors)

Systems(e.g. NEMS)

Nanotechnology isthe manipulation of matter at thenanometer* scale

to create novelstructures, devicesand systems.

5



Economic impact of nanotechnology

Market Size Predictions(within six years)

$340B/yr Materials

$300B/yr Electronics

$180B/yr Pharmaceuticals$100B/yr Chemical manufacture

$ 70B/yr Aerospace

$ 20B/yr Tools

$ 30B/yr Improved healthcare

$ 45B/yr Sustainability

$1 Trillion, growing to $2.6 Trillion by 2014

*Estimates by industry groups, source: NSF and LUX



Nano shirt, slacks, tie, tennis racket, odor/ bacteria eliminatingsocks, nano car wax, and 2004 Chevy Impala with nano enhanced

side panels.

7



Nanobiotechnology In Medical

Technologies

8

http://www.tatumpointanimalhosp.com/images/ultrasound.jpg

http://www.alnwickpharmacy.co.uk/images/tablets.jpg

http://www.carolinas.org/services/images/surgery.jpg

http://pt.uindy.edu/images/stethoscope.jpg

http://www.treathiv.com/graphics/4.patient_edu/4.11.syringe.jpg

http://www.scieng.ed.ac.uk/images/chembottles.jpg

http://www3.oup.co.uk/jnls/images/subject_graphics/medicine.jpg



Nanotechnology in Health

Care

Video Journey into NanotechnologyNational Cancer Institute, Alliance for Nanotechnology

in Cancer – http://nano.cancer.gov/resource_center/video_journey.asp

National Cancer Institute Video Journey Into Nanotechnology.flv

9



Nano-technology

Nanotechnology is a new field with many

possible uses, medicine being one of them.

Nanotech was first predicted by Nobel Laureate

Richard Feynman in 1959.It’s anything to do with structures one to several

hundred nanometers long in at least one

direction. However, nanotechnology doesn’t

necessarily deal with nanometers, as it can beexpanded to include structures measured in

microns also.

10



Present Major MedicalApplications

- Cardiovascular

- Drug delivery &Therapy

- Genetics

- Neurology

- Oncology

- Point of care diagnostics

- Surgery

- Tissue engineering- Prostheses

- Pathology

11



Size of Markets

• Drugs & Drug Delivery $80 billion

• Blood Analysis $22 billion

• Heart Pacemakers & $16 billion

Other Implants• Endoscopy & MIS Tools $5 billion

• Hearing Aids $4 billion

• DNA / Lab on Chip $1.2 billion

12



13

Drivers in healthcare

– Ageing population– Personalized health– Earlier diagnosis

– Cost of healthcare– Global travel (epidemics)– Food safety– Monitoring of individuals (glucose,

cholesterol)

– Ethics (eg stem cell research, animaltesting)



Hot R&D Topics

• Lab on Chip

• Retinal Implants

• Non Invasive Blood GlucoseMonitoaring

• The ‘Electronic Rat’

14



Timescales?

• Roadmaps based on– current status of R&D

– Future vision

– Past experience

• Balance market drivers againstbarriers

15



Nano molecular diagnostics

Nano chips/bio chipsNano arrays/protein nanoarrays

Drug discoveryGene therapy and RNAinterference

16



Method

Nano particle protein chip

Nano particles for molecular

diagnosticsNano arrays for molecular diagnostics

Nanotechnologies on biochips

17



Lab-on-a-chip systems are miniaturized biosensors that,coupled with

portable instruments, promise to offer inexpensive, point of care

medical diagnosis. The technology is being tested for use in the

monitoring of HIV immune function.

18



Lab-on-a-chip systems

Study of chromosomes by AFM

Application of nanopore technology formolecular diagnostics

DNA protein and nano particle conjugates

Nanoparticle based colorimetric DNAdetection method

Nanobiosensors

Nanowirebiosensors etc

19



Biobarcode assay for proteins

20

f



Instrument for DNADetection

21



Biosensors These are the biosensors under development in world-class laboratories. Some

of these devices were developed in collaboration with PPP model.

HandHeldmodel

Submersible

model

KinExA™model BenchTop

model

22

http://www.som.tulane.edu/labs/blake/images/biosensors/knx2.jpg

http://www.som.tulane.edu/labs/blake/images/biosensors/sbmsb2.jpg

http://www.som.tulane.edu/labs/blake/images/biosensors/bchtp3.jpg

http://www.som.tulane.edu/labs/blake/images/biosensors/hdhld1.jpg



NANOPLEX™ biomarkers are robust, patented opticaldetection labels that bring entirely new, much-needed

capabilities to clinical diagnostic and life sciencemeasurements.

23



Nanotechnology based biosensor prototype capable

of species-specific detection of microorganisms

24



Cantilever arrays QD

25



Applications

Diagnostics Using Sensors and Nano

Electro Mechanical Systems (NEMS) &

implants

Drug Delivery Using Nanoparticles and

Molecular Carriers

Lab on a Chip and Advanced Drug

Delivery Systems

26



Applications



Implants


Molecular Carriers


Delivery Systems

27



As diagnostics

• Biosensing

• Nanoarrays: genes and proteins

• Nanoparticle complexes of DNA and

peptides

28



Biological recognition elements

for sensorsEnzymes

-transformation of analyte into sensor detectable product

Antibody-antigens-high affinity binding with tracer to generate a signal

DNA-ligand binding

Biomimetic sensors-engineered molecules (single chain antibody fragment)

- supported lipid bilayers

-molecularly imprinted polymers

Whole cells or cellular structures-pollutant dependent inhibition/ activation of cell respiration

-membrane transport proteins-neuroreceptor proteins produce signal through ion channels

29

Fib ti h l t l



Fiber-optic cholesterol sensor

The enzyme cholesterol oxidase converts cholesterol

and oxygen to cholestenone and peroxide. The

change in oxygen is sensed by the decacyclene

fluorescence. B. Kuswandi et al., Analyst, 2001

30



Nanoarrays

Nanoarray with single-stranded DNA representing

thousands of different genes, each assigned to aspecific spots on a device.

Each spot includes thousands of to millions of copies

of a DNA strand

NANOARRAY

CHIP

31



DNA-nanoparticle complexes

•

•

DNA molecule

DNA-nanoparticlecomplexes basedon Au-thiolbinding

Nanoparticlelabeling for biochips

Labeling of singlemolecules

Devices, e.g.nanoelectronics.

•

•

•

33



DNA-coated gold nanoparticles (NPs) system

that also uses larger magnetic microparticles (MMPs) to detect

at tomolar (10-18) concentrations of serum proteins .

34



Nanotechnology and diagnostics

DendrimersDendrimers, 1- to 10-nanometer

spherical polymers of uniformmolecular weight made

from branched monomers (Poly

imido amine), are provingparticularly adept at providingmultifunctional modularity.

Dendrimers can serve as versatile

nanoscale platforms for creatingmultifunctional devices capableof detecting cancer and deliverydrugs.

35



Nanotechnology in observing

disease processes involving fibrils

using AFM

growth of beta-amyloid (->Alzheimer !) visualized by AFM36



Applications



Implants


Molecular Carriers


Delivery Systems

37



Drug encapsulation and delivery

with nanoparticles

•

••

•

••

vehicles for delivery

coated solid particles

vesiclesliposomes

micelles

polymerssolid lipid nanoparticles

38



Nanoparticle as Delivery System for Drugs

or Genes for Tissue and Cell

39



Intracellular trafficking of nanoparticles

Nanoparticles eventually act as intracellular

reservoirs for sustained release of encapsulated therapeutic agent.

•

40



Tissue targeting of nanoparticles

Cross section of pig coronary artery infused

with rhodamine B containing PLGAnanoparticles. Intense fluorescence indicates

deposition of nanoparticles in the arterial wall.

L=lumen, NP=nanoparticles, A= adventitia41



Block copolymer micelles for gene

therapy

Transfection of

plasmid DNA using

diblock copolymer.

DNA is released inside

the cytosol and

appears in the

nucleus to express adesired protein.

42



Cell microencapsulation in polymer

matrix

43

Enhanced Permeability and Retention



Enhanced Permeability and Retention

(EPR) effect)Nanoparticle entry and accumulation in tumors• PEGylated particles, in the desired size range, leaks out of the

microvasculature and accumulates into the tumor site.

Insufficient lymphatic drainage favors retention of PEGylatedParticles within the tumor site

•

44

Nanotechnology and cancer



Nanotechnology and cancer therapy

Silica coated lipid micelles

Silica-coated lipid

micelles containingLH-RH as a targeting

agent have been

used to deliver iron

oxide particles to LH-RH receptor- positive

cancer cells

45

Micellar Nano particles in cancer therapy



Micellar Nano-particles in cancer therapy

Lymphatic delivery

Tumor conc. of 99mTc labelledEtoposide and EPM 1, 6, 24

hours after S.C.Inj.12

10

8

6

4

2

0

Time (h)

Admn. Of etaposide loaded polysorbate 20 micellar

formulation (Right bar) by S.C. Inj. Enhanced the

tumor uptake in comparison to etoposide (Left bar)

Ref: Reddy & Murthy (2005) Acta Pharm.(In Press) 46



Poly Butyl Cyanoacrylate nanoparticles

loaded with Dox

• Prepared by dispersionpolymerization in DextranMedia

• Particle size: 100-300 nm

• Entrapment : 86-90%• Tumor Conc. Of 99mTc-

Dox and 99mTc-DPBCNano-particles in Dalton’slymphoma solid tumor

bearing mice

• Ref: Reddy & Murthy: J.Drug Targeting, 12(7),2004, 433-451

47



Nanostructured lipid carriers

• Phase separation

process during

cooling in solidlipid nanoparticle

(SLN) production

leading to a drug

enriched shell

48

Tumor accumulation Studies with



Tumor accumulation Studies with

Etoposide nanoparticles (ETPL)

• Tumor accumulation of 99mTc-Etoposide and 99mTc-

ETPL in Dalton’s lymphoma tumor bearing mice

• Radioactivity measured 1h, 6h and 24h after

subcutaneous administration

Ref: Reddy & Murthy:AAPS Journal, 6(3), Article 23, 2004

3

2

1

0

1a 1b 2a 2b

Time (h)

3a 3b

a : ET

b : ETPL

1 : 1h2 : 6h

3 : 24h

nanobiotechnology and its applications in medical diagnostics and biomedical field 1

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