Nanotechnology: Emerging Tool for Diagnostics and Therapeutics Jan Major Points from Appl Biochem Biotechnol (2011) 165:1178–1187

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

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

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

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

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)

MAGNETIC NANOPARTICLES Made from magnetic materials like Fe 3 O 4, Fe 2 O 3, 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

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

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

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

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 C 60 and dodeca-amino derivatized C 60 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

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

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

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

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

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

Three Dimensional View