He never set out to be the Man with the Midas Touch. In 2004, biochemist Debabrata Mukhopadhyay, Ph.D., came to Rochester, Minn. to lead a team researching blood-vessel growth. But now, as an offshoot of that work, his lab also is investigating the use of minute gold particles to treat cancer, and other elements to treat heart disease. No James Bond villain, Dr. Mukhopadhyay pioneers in the branch of health care called "nanomedicine."

Precious metals

Nanomedicine uses nanoparticles—bits of metal measured on a scale of billionths of a meter—for smarter intervention in life-threatening diseases. Roughly 100,000 times smaller than the width of a human hair, nanoparticles pack a lot of therapeutic power: Lab tests indicate they can boost drug efficacy and improve drug targeting to specific areas in the body, making treatment less toxic and invasive. The significance for fighting cancer and other diseases is profound, particularly for patients with limited treatment options.

"I am really excited that this technique indeed holds promise," says Suresh Chari, M.D., a gastroenterologist who researches pancreatic cancer. A leading cause of cancer deaths, pancreatic cancer spreads rapidly and is very difficult to treat. "I am tired of telling my patients to go home and die because I have nothing to offer them," Dr. Chari adds. "It's depressing." He is eager for patients to participate in clinical trials of the nanoparticle treatment: "We are ready to go, as soon as we have the drug in our hand."

Dr. Chari was among several physicians who encouraged Dr. Mukhopadhyay to pursue nanomedical research at Mayo. "He kept telling me, ‘Do something, because people are dying,'" Dr. Mukhopadhyay recalls. "That's the beauty of Mayo Clinic. We can see the importance of the research we do. We can translate it into patient care as soon as possible. We need an arsenal to fight these deadly diseases."

Nanomedicine looks like a major weapon in that arsenal. "It has tremendous implications for human health care," says Priyabrata Mukherjee, Ph.D., the key nanotechnologist on Dr. Mukhopadhyay's team. "It's the future of medicine."

It's also the past, at least when the nanoparticles are gold. "Five thousand years ago in India, they used gold nanoparticles" to treat blood diseases and arthritis, notes Dr. Mukhopadhyay, who grew up near Kolkata (formerly known as Calcutta). The gold was purified into an ash, which was consumed without knowledge of its nano-characteristics.

The modern era of nanomedical research began in 1983, with the development of sophisticated microscopes that allow researchers to see nanoparticles. Mayo's program dates to Dr. Mukhopadhyay's arrival four years ago. Since then, he has assembled a team of more than 20 researchers who he says "have changed the whole dogma of nanoparticles. We now know a lot of basic science about nanoparticles and how they really work."

Gold bullets search and destroy cancer

Gold nanoparticles may be ideal for delivering anti-cancer drugs. They have a large surface area and strong bonding properties, allowing researchers to load onto them anti-cancer drugs as well as agents that target drug delivery to a specific disease site. Gold's bonding properties also help the drugs stay on site rather than dissociate into the bloodstream.

Think of a nanoparticle as a gold bullet fired directly at a tumor, rather than shot pellets scattered at random throughout the body. That precision means the overall drug dose can be lowered resulting in fewer side effects. In lab tests Dr. Mukherjee found that one-tenth of the normal pancreatic-cancer drug dosage, when combined with gold nanoparticles, is more effective against the disease than the full dosage used alone.

"This discovery has huge promise," Dr. Mukherjee says, "not only to reduce the cancer, but to reduce the systemic toxicity immensely."

It also might halt a rapidly spreading cancer. Lab studies indicate the nanoparticles can carry a "homing device" that sends anti-cancer drugs to the tumor no matter where it is located. "It may be a way to search and destroy the cancer everywhere," says Dr. Chari. That would be particularly significant for pancreatic cancer, which often spreads beyond the pancreas before the disease is diagnosed.

Mayo's research on gold nanoparticles "will change the face of nanomedicine," Dr. Mukhopadhyay says. "I am very confident about that." Besides pancreatic cancer, gold nanoparticles show promise for treating leukemia, multiple myeloma and ovarian cancer, he adds.

Nanorods grow new heart vessels

Cardiovascular disease is yet another target for nanomedicine based on work done by a third researcher on the Mukhopadhyay team. Chittaranjan Patra, Ph.D., used a domestic microwave oven to synthesize an inorganic fluorescent nanorod which, when injected into human tissue in the lab, can label live cells. This piece of matter, which comes from the lanthanide group of elements rather than gold, is called a "nanorod" because of its characteristic shape.

Unlike traditional organic fluorescent dyes, which can damage cells, the inorganic nanorod "is not toxic at all," Dr. Patra says. It has a longer lifespan than organic dyes, isn't subject to photobleaching and, best of all, can grow new blood vessels from existing ones: "an excellent therapeutic target for the treatment of cardiovascular disease."

"This is a huge implication," Dr. Mukhopadhyay notes. "We've got nanorods which can make new blood vessels." These blood vessels are "much more mature" and lack the edema often associated with blood vessels grown using current methods, he adds. Mayo has a patent on the nanorod material and hopes to begin clinical trials.

For Dr. Mukhopadhyay, nanomedicine is an outgrowth of his primary research interest: angiogenesis, or the growth of new blood vessels. Recruited from Harvard University to lead Mayo's angiogenesis research, he quickly found Mayo to be an "extraordinary" place to work. "When I moved here, I met so many good clinicians who are eager to move forward from the (research) bench to the (patient) bedside," he says.

"Mayo is a unique place for nanomedicine. That's why I came here," agrees Dr. Mukherjee, who followed Dr. Mukhopadhyay to Rochester from Harvard. "I want to apply nanomedicine to human health care. We have all the state-of-the-art facilities for research and for human health care. That is why we can move faster."

Moving the lab work to clinical trials is a top priority for Dr. Mukhopadhyay. When he arrived at Mayo, he recalls doctors' persistently asking when nanomedical therapies might be available for patient use. Initially, Dr. Mukhopadhyay says, that day "was kind of far off. "Now I can see the light at the end of the tunnel."

All this in just four years from a man hired to run a blood-vessel research lab. By the way, that angiogenesis program is thriving under Dr. Mukhopadhyay. The nanomedicine program is a bonus: "like, buy one, get one free," he says with a laugh.

—Barbara Toman, September 2008