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Uri Sagman is not your average bomb builder. An Israeli-born, Canadian-trained oncologist, he spent the early years of his career treating cancer patients, watching many suffer the ravages of chemotherapy and radiation, only to die anyway. "At least once a week I went home in tears," says Sagman. "I kept thinking there had to be a better way." Today Sagman, 47, is president of C Sixty, a Toronto-based nanotechnology company that is developing carbon molecules called fullerenes as a drug-delivery system for cancer, AIDS and other diseases. Soon, he hopes, it will be possible to load these minuscule, spherical structures--each containing 60 carbon atoms arranged like the hexagonal pattern on a soccer ball--with drugs or radioactive atoms and then fire them like guided missiles at diseased cells. "Think of a smart bomb," says Sagman. "Conventional chemotherapy is like carpet-bombing. You drop it from 60,000 feet and hope for the best. This goes precisely to the target."
Once the province of science fiction, nanotechnology, the science of assembling materials one atom at a time, is now the rage among Silicon Valley investors. "Nano," from the Greek prefix for "one billionth," requires an unimaginably tiny scale; a million or so fullerenes could fit into a grain of rice. Named after the architect Buckminster Fuller, whose geodesic dome the fullerene resembles, the sturdy carbon molecule (also nicknamed buckyball) has emerged as one of the most versatile tools in the rapidly developing nanotechnology arsenal. An elongated chemical cousin called the buckytube is also showing great promise. While computing breakthroughs such as molecular circuits may not be commercially available for another decade, the first devices for nanoscale drug delivery will enter clinical trials later this year.
At C Sixty, Sagman and his colleagues insert drug-coated fullerenes inside the virus that causes AIDS to prevent it from reproducing. Unlike traditional HIV therapies, the fullerenes are also effective in combating the virus as it mutates during treatment. To treat cancer cells, researchers "decorate" the surface of fullerenes or larger carbon units known as "buckysomes" with chemotherapeutic agents. Then they attach an antibody, which serves as a guidance system. Fully loaded, the molecule resembles a pincushion. The antibody detects the unique chemical signature of a cancer cell and propels the fullerene directly to the surface of the tumor, where it delivers its payload. "The fullerene goes like a bomb right through the chimney," says Dr. Michael Rosenblum, of the University of Texas M.D. Anderson Cancer Center in Houston. "The drugs don't go where they cause toxic reactions, such as hair falling out and gastric upsets."
The pioneers of nanotech drug delivery describe their work in terms that would make Donald Rumsfeld proud. By targeting individual cells instead of tissues or organs, nanotechnology opens a battlefield of exploding atoms, molecular missiles and pint-size Trojan horses in the war against disease. But there are still some Pentagon-size headaches ahead. The biggest challenge is finding a reliable, affordable method of connecting the steering system to the payload. For the past year, scientists at M.D. Anderson have been seeking ways to bind antibodies to fullerenes. "Once we do, we're off to the races," says Rosenblum. In the meantime, he cautions, cancer patients should not see nanoscale drug delivery as a magic bullet. While the research is very promising, says Rosenblum, not yet enough data are available to conclude that nanotechnology is better than forms of targeted drug delivery already on the market.
At Houston's Rice University, where physicist Richard Smalley discovered the fullerene in 1985 (and in 1996 shared the Nobel Prize for his achievement), researchers have developed another platform for nanoscale drug delivery called the nanoshell. Unlike fullerenes, which are made of carbon, the slightly larger nanoshells are hollow spheres made of silica and coated with gold, giving them unique optical and conducting properties. The nanoshells are embedded in a drug- containing polymer and injected into the body. When heated with an infrared laser, the nanoshells make the polymer melt and release their drug payload at a specific site.
This technique could prove useful in treating diabetes. Instead of taking an injection of insulin, a patient would use a ballpoint-pen-size infrared laser to heat the skin where the nanoshell polymer had been injected. The heat from nanoshells would cause the polymer to release a pulse of insulin. Unlike injections, which are taken several times a day, the nanoshell-polymer system could remain in the body for months.
Last year Rice licensed its nanoshell technology to a private company, Nanospectra Biosciences, to develop commercial applications. At the company's Houston headquarters, scientists are also developing a new form of cancer treatment called photothermal destruction. The idea is for nanoshells to carry radioactive particles to the cancer cells and, in essence, blow them up--a process that Nanospectra president Donald Payne likens to "a tiny, remote-controlled nuclear explosion"--giving patients the benefits of radiation therapy without the side effects. The company hopes to start clinical trials for the cancer treatment by 2004, and for the insulin-delivery system by 2006.
At NTera, a new nanotechnology company in Dublin, scientists are seeking ways to infiltrate brain cells using minuscule, concentrated drug particles called nanocrystals. Like fullerenes and nanoshells, nanocrystals are coated with antibodies that will steer them to diseased cells. Their potential lies in treating neurological diseases, such as multiple sclerosis and Alzheimer's, as well as brain cancers, because they are small enough to slip through the blood-brain barrier. After delivering drugs to the diseased brain cells, the crystals return to the bloodstream. According to NTera's Ivan Coulter, "they should go in, do their jobs and get out."
The nanoscale drug-delivery systems that pass clinical trials could be on the market in five to 10 years. While nanotechnology doesn't offer a cure for cancer, millions hope the tiny molecules live up to their giant potential. No one knows this better than Smalley, the Nobel Prize winner who helped launch the era of nano-medicine in 1985. Three years ago he was diagnosed with lymphoma, an often fatal cancer of the circulatory system. His illness is currently in remission. Smalley says even he doesn't know if the carbon spheres he stumbled upon could someday save patients like himself. "It may be decades before all this plays out," he says. "But if the buckyball is part of making cancer history, that would be great."