Nanomedicine for Cancer Prevention

By Curtis Gibson

Nanomedicine• Involves particles on a nanoscale level• Can carry tens of thousands of small

substances– Drugs for treatment delivery– Contrast agents for imaging

• Major areas of use for cancer– Prevention and control– Early detection and proteomes– Imaging diagnostics– Multifunctional therapeutics

Nanomedicine Size

• Typically between 10 and 100 nanometers

Nanowires

• Act as sensors by detecting cancer proteins• Conductive wires laid along a channel for

sample particles to flow through• Use probes such as antibodies or DNA• Complimentary antigens or DNA from the

tumor bind to the probes• Reaction changes electrical conductivity• Monitored by an electronic detector• Nanowire animation

Cantilevers

• Also used as sensors• Beams of semiconductive material containing

probes• Complementary DNA or proteins from the tumor

bind to probes• Reaction causes cantilevers to bend slightly• Can even recognize when a single DNA molecule

or protein attaches• Process can also be observed electronically• Cantilever animation

Quantum Dots

• Used for magnetic resonance imaging• Nanocrystals of semiconductor material• Often cadmium or mercury containing

compounds covered with metal or latex• Emit light at certain wavelengths and

frequencies• Antibody-antigen complex• Illumination of the dots changes creating a

marker for cancer proteins

Nanoshells

• Used for imaging and cancer tissue targeting• Composed of a solid core of silica with a

surrounding thin metallic layer, often gold• Enter tumor tissue by large pores in the irregular

blood vessel walls• Absorb light in the NIR region and convert this to

heat destroying cancer cells• Antibodies may also be attached to nanoshells to

promote tumor specificity• Nanoshell animation

Nanospheres vs Nanocapsules

• Nanospheres– Polymeric matrix with drug covalently bonded

and scattered throughout• Nanocapsules– Aqueous or oily core with drug enclosed by a

single polymeric membrane• Poly(isobutylcyanoacrylate) for hydrophobic

drugs• Poly(ethylene glycol) for hydrophilic drugs

Micelles

• Polymeric nanoparticles• Hydrophobic core surrounded by hydrophilic

shell• Water soluble and delivered by IVs• Drugs can be covalently bonded to the core

or exclusively trapped inside by physical means

Dendrimers

• Macromolecules composed of multiple branched polymers emerging for a single radial center

• Polymers are all similar in size and are about 1 to 10 nanometers long

• Can adjust their surface functionality and can even contain different charges on polymers

• Treatment agents can be stored inside the core or attached to polymers outside

Liposomes

• Lipid-based drug carriers that are spherical• Contain an outer lipid bilayer that encloses

an aqueous inner space• Lipid shells allow liposomes to passively

travel through cancer membranes• Therapeutic particles contained in the inner

core

Viral Nanoparticles and Nanotubes

• Viral nanoparticles– Virus contains antibodies on capsid surface– Drugs contained inside the capsid– Can be combined with fullerenes (C60) to make an

even better molecule for delivery• Nanotubes– Cylinders formed from benzene rings– Insoluble but can be made soluble through

chemical modifications– Multiple different functional areas on sidewalls and

ends

Obstacles of Nanoparticles

• Obstacles– Surviving in the bloodstream– Selectively entering tumor cells

• Requirements– Must be large enough to avoid escaping into

capillaries– Must be small enough to avoid being ingested by

macrophages in the reticuloendothelial system– Must have a hydrophilic region to keep proteins

from recognizing them as foreign particles

Passive Targeting

• Enhanced permeability and retention effect– Cancer cells have a constant need for oxygen and

nutrients– Matrix metalloproteins and other enzymes become

imbalanced– Results in multiple disorganized pores in tumor blood

vessels and inflated gap junctions between endothelial cells

• Microenvironment of the tumor– Cancer cells use glycolysis to provide nutrients– Acidic environment is created– pH-sensitive nanoparticles

Active Targeting

• Antigen expression of the tumor– Involves linking antibodies with nanoparticles

that will bind with tumor antigens– Antibodies linked directly to drugs were not

successful– Complimentary surface receptors must be

located only on cancerous cells– Receptors must be expressed equally on all

target cells– Receptors must never be shed into bloodstream

Active Targeting

• Internalization of nanoparticles– Ligand binds to receptor on tumor surface– Plasma membrane invaginates forming an

endosome– Endosomes transported to target organelles– Bond between drugs and nanoparticles are

broken by either hydrolysis or enzymes– Lysozymes are triggered when pH becomes acidic– Process bypasses protein pumps such as

glycoprotein P

Ligands to Target Cancer

• Vitamin folate– Water-soluble vitamin from the B complex

• Tranferrin– Serum glycoprotein that carriers iron through

bloodstream into cells• Apatamers– Linked strands of oligonucleic acids (DNA or RNA)– Unique three-dimensional structures

• Lectins– Proteins that attach to glycans on plasma membrane

Where is all this going?

• More personalized and effective methods of treating cancer

• Avoiding harmful side-effects by targeting only tumor tissue

• Cost efficiency• Viewing cancer as a network of interrelated

events and not just as a pathway of events• Creating the ultimate nanoparticle capable of

doing everything other nanoparticles can do

References• Cho, K., Wang, X., Nie, S., Chen, Z., & Shin, D. M. (2008). Therapeutic

nanoparticles for drug delivery in cancer. Clinical Cancer Research, 14(5). doi: 10.1158/1078-0432.CCR-07-1441

• Heath, J. R., Davis, M. E., & Hood, L. (2009, February). Nanomedicine targets cancer. Scientific American, 44-51.

• Heath, J. R., & Davis, M. E. (2008). Nanotechnology and cancer. Annual Review of Medicine, 59, 251-265. doi:10.1146/annurev.med.59.061506.185523

• Poh Hui, N. C. (2005). Nanomedicine and cancer. Retrieved October 22, 2009, from http://www.tahan.com/charlie/nanosociety/course201/nanos/NH.pdf

• Steinmetz, N. F., Hong, V., Spoerke, E. D., Lu, P., Breitenkamp, K., Finn, M. G., et al. (2009). Buckyballs Meet Viral Nanoparticles: Candidates for Biomedicine [Electronic version]. Journal of the American Chemical Society, 131(47), 17093-17095. doi:10.1021/ja902293w