Nanotechnology: Emerging Tool for Diagnostics and Therapeutics

Jan. 2013Major 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 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

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 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

• 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