Nanomedicine for Cancer Prevention

1. Nanomedicine for Cancer Prevention By Curtis Gibson

2. 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

3. Nanomedicine Size • Typically between 10 and 100 nanometers

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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