Nanotechnology : Emerging Tool for Diagnostics and Therapeutics

1. Nanotechnology: Emerging Tool for Diagnostics and Therapeutics Jan. 2013 Major Points from ApplBiochemBiotechnol (2011) 165:1178–1187

2. Design of Nanomaterials • “Top down” approach: breaking down larger particles to nanoscale • ball-milling process, ion beam lithography, electron beam lithography • Patterning on a surface; used as a mold • “bottom up”: built up from the elemental constituents • chemical self-assembly, artificial synthesis techniques

3. PRIMARY NANOMEDICINE APPLICATIONS • Disease diagnosis • Efficient, specific, and safe (reduced toxicity) drug delivery systems NOTE: small size means they are not easily recognized by the body’s immune system

4. NANOPARTICLE TYPES FOR DRUG DELIVERY Wide variety • Liposomes • Inorganic nanoparticles: gold, ferrites • Dendrimers • Polymeric nanoparticles Used for detection, magnetic resonance imaging, tumor destruction

5. NANOPARTICLES WANT THEM TO: • attach a variety of ligands WHY? • interact with cells and tissues with a high degree of specificity WHY?

6. GOLD NANOPARTICLES • top down approach: • Reduction of gold salts • associate with stabilizer that provides good ligand binding • Have electronic, optical, and thermal properties • 3 and 100 nm are stable • Modify properties via chemical modification of surface • interaction with target molecules subtle emission spectra changes • Applications: diagnostics and detection of biological molecules at low concentration (fmolar)

7. MAGNETIC NANOPARTICLES • Made from magnetic materials like Fe3O4, Fe2O3, and many other ferrite molecules via co-precipitation, thermal decomposition and reduction, micelles synthesis • Associated with biorecognition molecules so that they can be used to detect different biomolecules and help in processes like separation and purification • Surface coatings determine size and kinetics • Issue: susceptible to corrosion, i.e., rust; must be protected via coating surface with non-toxic and biocompatible polymers, silica, or carbon • Applications: magnetic immunoassays, drug delivery, cell separation, purification, and tissue repair

8. QUANTUM DOT NANOPARTICLES • semiconductor nanocrystals • easy to synthesize • 2 to 10 nm diameters • quantized energy levels • fluorescent properties are size dependent • As size decreases, band gap increases greater energy difference between the conduction band and valence band • Size decreases requires more energy to excite the dot • energy released is higher when dot returns to ground state  light has higher frequency • broad range of excitation wavelengths multitude of colors • Applications: imaging and detection; localize at tumor sites

9. CARBON NANOTUBES • graphite • members of fullerene structural family • composed of sp2 bonds which are stronger than sp3 bonds • Do not break when bent just change structure • Forms cylindrical nanostructure; few nm diameter • novel electrical, chemical, and mechanical properties • 2 types both transport electrons; carry high currents with little heating • single walled carbon nanotubes: single layer of graphite • Multi-walled carbon nanotubes – single layers inside of each other • Applications: detection, monitoring, and disease therapy EXAMPLE: antifungal drug amphotericin B  enhanced biological action and decreased toxicity

10. Diagnostic agents, delivery agents, antioxidants, and finally their function as antimicrobial and antiviral agents • IMAGING • Magnetic resonance imaging (MRI) • x-ray • Radio imaging

11. Delivery drugs and genes • fullerene–paclitaxel conjugate designed to release paclitaxel via enzymatic hydrolysis following aerosol liposome delivery as a slow-release drug for lung cancer therapy • Octa-amino derivatized C60 and dodeca-amino derivatized C60 molecules developed as DNA/gene-delivery vectors • tissue-vectored bisphosphonate fullerene developed as an osteoporosis drug • Scavenge free radicals: neurodegenerative disorders – Parkinson’s & amyotrophic lateral sclerosis

13. Many types of polymers are widely used in biomedical applications that include dental, soft tissue, orthopedic, cardiovascular implants, contact lenses, artificial skin, artificial pancreas, and drug and gene delivery

15. LIPOSOMES • spherical vesicles: aqueous core surrounded by a phospholipid bilayer and cholesterol • uniform particle size which is in the range of 50–700 nm and • special surface characteristics • Metastable; add surface polyethylene glycol to stabilize & prevent clearance • Classified on basis of size and number of layers as: • small unilamellar, large unilamellar, small multilamellar, and large multilamellar • APPLICATION: imaging, drug delivery

16. FLODOTS • organic or inorganic luminescent dyes are introduced in a silica matrix • surface modification with biodetection molecules allows use for detection • Better than quantum dots • APPLICATION: diagnostics, detection and bioanalysis • Examples: antibodies against Escherichia coli O157:H7 were conjugated with dye-doped silica nanoparticles

17. DENDRIMERS • Large, complex molecules with branches around an inner core, i.e., star shaped • Flexible: change size, shape, branching length, and their surface functionality • Polyamidoamine used for targeted delivery of drugs and other therapeutic agent (available commercially) • Load drugs inside or covalently bond to outside structure • Surface modified used against viruses and bacteria • dendrimer-derived microbicide (Vivagel) against HIV and genital herpes • APPLICATION: MRI-contrast agent; Increase drug solubility; chemical catalysts

18. DENDRIMERS – Three components • initiator core • Interior layers (generations) composed of repeating units, radically attached to the interior core • Exterior (terminal functionality) attached to the outermost interior generations

19. Three Dimensional View