Chicago Tribune - September 14, 2004
Ronald Kotulak, Tribune science reporter

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 Monday 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 that 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 1/80,000th 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 that 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 Richard Smalley, a Nobel laureate and professor of nanotechnology at Rice University who attended the announcement in Washington, D.C. 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 ones 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 that 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 and formed by Northwestern scientists, markets the gene-spotting particle.

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

Dr. Ralph Weichselbaum, chief of radiation oncology at the University of Chicago, and Vigi 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.

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