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