Nano Medicine (long Article but amazing!)

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Posted on Fri, Oct. 01, 2004

Tiny battlefield in the war on disease Devices as small as genes

detect, fight illnesses

BY RONALD KOTULAK

Chicago Tribune

CHICAGO - (KRT) - To the incredibly tiny gold particles doctors send

to search a blood sample for signs of illness, human cells would

seem as big as mountains.

But the particles' mission is to hunt down something more their

size: prostate specific antigen, or PSA, a signal that prostate

cancer may be on its way to returning - long before it actually does.

Welcome to the new frontier of nanotechnology, where scientists are

learning how to make super-small devices - as small as genes and

proteins - to diagnose diseases that remain unseen with present

equipment and to provide treatments tailored to affect individual

cells.

" The particles go into a blood sample, and if there are as few as 10

molecules of PSA present they will find them, " said Chad Mirkin,

director of Northwestern University's Institute for

Nanotechnology. " The current test would need 10 million molecules of

PSA to record a positive reading. "

Capitalizing on the promise of the field, the National Cancer

Institute announced Sept. 13 a $144.3 million program to establish

the National Nanotechnology Standardization Laboratory and to set up

at least five nanotechnology research centers across the nation.

Experts hope the field will produce new ways for detecting,

diagnosing, treating and preventing cancer in the next five to 15

years.

Many nanotechnology projects are under way at research institutions

across the nation, with Northwestern playing a major role in the

field.

The technology involves the construction of tiny tools that can be

designed to carry almost any type of gene or protein and designed to

target specific locations in the body. The devices are made of

different inorganic materials and engineered into optimal shapes,

including capsules, tubes and flattened pieces with many prongs.

A nanometer is one-billionth of a meter_or [0,000th the width of a

human hair. Ten hydrogen atoms in a row, the smallest atoms known,

make up a nanometer. Most human cells are 10,000 to 20,000

nanometers in diameter, which means nanodevices of less than 100

nanometers across can get inside cells and latch on to specific

genes and proteins. Larger devices can glide harmlessly through the

body and attach to the surfaces of targeted cells.

The field has the potential to benefit all areas of medicine, said

Smalley, a Nobel laureate and professor of nanotechnology at

Rice University who attended the announcement in Washington. It has

the possibility, he said, of monitoring the approximately 30,000

different types of proteins found in the body to determine the first

hint of something going wrong before trouble appears.

Northwestern's experimental gold particle test, for example, is a

million times more sensitive than the tests now in use to measure

PSA. Such an early alert system can prompt doctors to initiate

treatment to stop cancer from regaining a foothold in patients who

have had their prostates removed.

The precision with which the particles home in on cancer cells is

also enabling researchers at Northwestern's Medical School to work

on developing drugs to ride along with the particles and destroy

malignant prostate cells where they live.

" Nanotechnology can completely change the way we think about

diagnosing many forms of cancer, " Mirkin said. " We can now begin to

look at markers that the rest of the world can't even touch with the

old technology. It's opening up many avenues that could lead to

major advances in terms of treating cancer. "

Science is learning more about the human body on a smaller and

smaller scale. The genetics revolution, for example, is revealing

genes that cause disease or predispose people to certain ailments,

while biologists are discovering protein molecules that are critical

for maintaining health as well as molecules that drive disease

processes.

Because nanotechnology is such a recent science, doctors have not

had tools small enough to work in this ultrasmall universe.

Everything physicians use now is huge by comparison.

Drugs work at the cellular level because of their natural ability to

dissolve in liquids. But the drawback is medications often affect

healthy cells as well as diseased ones, creating the risk of adverse

effects.

For the last decade, scientists have been trying with limited

success to develop so-called " smart drugs " that could be directed to

specific tissue. Researchers say the nanotechnology developed in the

last five years has a much better chance of achieving the same goal

by engineering metals and other inorganic substances to target and

deliver treatment.

The first such products are already turning up in hospitals. One

version of Northwestern's gold nanoparticles is able to detect a

specific gene that can determine if a patient is prone to excessive

bleeding. The test, based on a blood sample, is simple and fast and

allows surgeons to quickly tailor surgery to reduce the risk.

Nanosphere Inc., a startup company based in Northbrook, Ill., and

formed by Northwestern scientists, markets the gene-spotting

particle.

In developing tools to work on this scale, scientists were surprised

to find material shrunk to sizes below 100 nanometers takes on new

properties. Gold particles of different sizes, for instance, will

emit different colors when exposed to ultraviolet light, a feature

that can be used to identify them.

The particles are coated with bits of DNA or antibodies that enable

them to hook up only with a particular target.

" By making groups of these particles that can recognize proteins or

DNA markers associated with disease, you can design them to detect

just about anything, ranging from Alzheimer's disease to different

forms of cancer, HIV, genetic diseases, all sorts of sexually

transmitted diseases and genetic predispositions to disease, " Mirkin

said.

A top goal of researchers is the development of cancer nanobombs,

tiny particles that seek out and destroy cancer cells.

Ralph Weichselbaum, chief of radiation oncology at the University of

Chicago, and Viji Balasubramanian of the Illinois Institute of

Technology are collaborating on a project to incorporate a cancer-

killer gene into a nanocapsule.

The gene makes tumor necrosis factor, which is toxic not only to

cancer cells but to healthy cells when injected in big doses. To

avoid damage to normal tissue, the nanocapsule is coated with

sensors that zero in only on tumor cells. A patient would then be

exposed to low-dose radiation or drugs that trigger the gene to make

the necrosis factor.

The research is in a preliminary stage, but looks promising,

Weichselbaum said. " The bottom line is that nanotechnology has a lot

of potential, " he said. " I'm cautiously optimistic. "

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New test could detect diseases at minute level

Scientists at Northwestern University are using gold nanoparticles

to measure minute quantities of disease markers. The test could be

useful in detecting recurrence of diseases, such as prostate cancer.

HOW THE TEST WORKS

To detect prostate specific antigens (PSA), markers for prostate

cancer

1. Blood sample is drawn from the patient.

2. Magnetic particles with antibodies that recognize PSA molecules

are added. If a PSA molecule is present, it attaches to the

antibodies.

3. Nanoparticles coated with synthetic DNA strands are added and

latch onto the PSA molecule.

4. A magnetic field is applied to draw the cluster of particles to

one side of the test tube while a salt solution washes away the

remaining sample.

5. Heat releases the DNA strands. For every PSA molecule captured,

thousands of DNA strands are released. A DNA detection device

analyzes information from the strands to determine the presence of

prostate cancer cells.

Source: Chad Mirkin, Institute for Nanotechnology, Northwestern

University

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© 2004, Chicago Tribune.

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