nanotechnology (1st draft)
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Medical Applications of Nanotechnology
Gholamreza Pourmand, M.D.
How small is nano?
Decade: 1/3rd second
Acre: 1/100th square inch
$151,700: 1/100th cent
Scale:Nanoscale
E. Corcoran. The Next Small Thing.Forbes Magazine, 07/23/01
Nanotechnology Growth
S. Milunovich, J. Roy. United States Technology Strategy. Merrill Lynch. 4 Sept. 2001
Smart Nanostructures for Selective Drug Delivery
Scale: 1/40th of red blood cell
Nanotube
Nanocap
Drug Delivery for:
#1 - Cardiovascular disease#2 – Cancer
#3 - Infectious diseases
Toxin Removal for:Adverse drug reactions >106,000 deaths/yr
Pesticide Poisonings >220,000 deaths/yr
NanoMedical Diagnostics
Targets: - drug overdose - brain trauma - disease markers
Where: - hospital - law enforcement - homeland security
What is nanotechnology
• Creation of functional materials, devices, and systems.
• Control of matter on the nanometer (1-100 nm) length scale.
• Exploitation of novel properties and phenomena developed at that scale.
What is nano?
nanos: dwarfnano 10-9
mikros: smallmicro 10-6
milli: thousandmilli 10-3
chilioi: thousand
kilo 103
megas: largemega 106
gigas: giantgiga 109
teras: monstertera 1012
OriginsPrefixPower
Why is the nanometer scale different?
1. The wavelike properties of electrons inside matter are influenced by variations on the nanometer scale.
2. The systematic organization of matter on the nanometer length scale is a key feature of biological systems.
3. Nanoscale components have very high surface areas.4. The finite size of material entities, determine an increase of the
relative importance of surface tension and local electromagnetic effects.
5. The interaction wavelength scales of various external wave phenomena become comparable to the material entity size.
Targeted Delivery to Tumors
Many Different Length Scales
10cm
1cm
100m
1m
Relative Size of Nanoparticles
Nanoparticle with a 2 nm core and an octanethiol functionalized monolayer
Making Gold Nanoparticles
• AuCl4- salts are reduced using NaBH4 in the presence of thiol capping ligands
• The core size of the particles formed can be varied from <1 nm to ~ 8 nm
• The surface functionality can be controlled through the choice of thiols
Fluorophores and Drugs Selectively Dissociate Inside
Cells
Control of Surface Charge
Investigating Delivery Using Cylindroids
100 mPlug
WellPlate
MicroscopeObjective
Cylindroid
Viable
Dead
Nanoparticles in Cylindroids
How Does Particle Charge Affect Tissue Penetration?
Transcellular
Paracellular
Cells
A
B
Engineering Approach:Targeted Intratumoral
Therapy
• Quantify tumor microenvironments
• Develop vectors to target tumor quiescence
NecroticQuiescentProliferating
Therapeutic
Tumor Growth and Mouse Survival
PBSControl BacteriaCytotoxic Bacteria
PBS + 2GyControl Bacteria + 2GyCytotoxic Bacteria + 2Gy
Cytotoxic Bacteria Control Bacteria
PBS
Bacteria + RadiationControl + 2GyPBS + 2Gy
Median survival doubles from 14.0 to 26.0 days
Cells
A
B C