The next big nano thing
Will tiny tubes pull off medical miracles?
By ANNE PINCKARD
Hongjie Dai, PhD, wasn’t sure what to expect when five years ago he mixed proteins with tiny tubes made of carbon. Few before him had tried anything similar. “We were driven by curiosity,” he says.
Dai, a professor of chemistry at Stanford, had been studying the unusual physical and electrical properties of the tiny carbon particles called single-walled carbon nanotubes. He reasoned, if there was a way these tubes could help fight disease, he should try to find it.
Dai’s work exemplifies a growing interest in technology on the scale of a nanometer, or one-billionth of a meter — about 1/80,000 the width of a human hair. Called nanotechnology, the field spans physics, electronics, chemistry and, in the last 15 years, medicine. In 2003, Congress passed a bill authorizing $3.7 billion to fund nanotechnology research, including medical applications. This year witnessed the launch of the National Cancer Institute-funded Center of Cancer Nanotechnology Excellence at Stanford, of which Dai is a member. And in August the Food and Drug Administration created an internal task force to assess the state of nanotechnology in medicine and recommend a future course.
Why the excitement? Nanotechnology promises diagnosis and therapy tailored to a patient’s genes and delivered with precision never before possible. For instance, by injecting sensors made of nanoparticles into the bloodstream, scientists will be able to continuously measure glucose levels for diabetics, or keep tabs on neurons at risk for Alzheimer’s disease. They’ll be able to detect problematic cells before a disease even has a chance to develop, and destroy them without harming any others. At least, that’s the theory.
Mixing nano with bio
“With nanomaterials, we can interact with molecules,” says James Baker, MD, director of the Michigan Nanotechnology Institute for Medicine and Biological Sciences at the University of Michigan. “Their unique capabilities present potential, but also create issues — for instance, they can be absorbed across the skin because they can penetrate and go through pores.”
Dai’s pioneering experiment mixing nanotubes with biological molecules revealed that proteins attach to the tubes’ smooth, curved walls: a promising sign. For the biomedical applications he had in mind, it was important that nanotubes and proteins — the workhorses of biology — interact.
In the few years since that discovery, the field of carbon nanotubes in medicine has exploded. Already, researchers are using carbon nanotubes to build scaffolds for artificial bone and muscle and to serve as an interface between neural tissue and prosthetic electronics. But as the technology becomes more prevalent, fears have escalated. Environmental watchdog organizations including the Canada-based ETC Group cite studies claiming nanotubes damage lungs when inhaled. And they might carry unwanted material with them when they slip inside a cell. Furthermore, nanotubes can clump and clog up biological systems. Still, most evidence suggests that medical applications of nanotubes will be benign. Currently, the FDA provides no additional restrictions or guidelines when reviewing therapies based on nanotechnology.
Since their discovery in 1991, carbon nanotubes have been used for almost everything, from water desalination, to solar cells and light bulbs, to super-strong fabrics. Their strength surpasses steel, and their conductivity is 1,000 times greater than that of copper.
Dai harnessed their electrical properties to develop a cancer detection method much more sensitive than conventional means. He studded nanotubes with molecules that lock onto cancer-indicating substances in tissue or blood samples. Once bound, the nanotubes lose some conductivity. As a result, a test of a sample’s conductivity can reveal cancer’s presence. More recently, Dai became the first to show that the tubes’ unique optical pro-perties could be used to destroy the cancer cells as well. The tubes absorb near-infrared light, an important spectrum in medicine because it penetrates living tissue harmlessly.
Dai engineered the nanotubes to latch onto cancer cells in solution and then cooked the cancer cells to death by bathing them in the light of a near-infrared laser beam. The highly selective approach could replace dangerous chemotherapies.
Rendezvous with the inner tubes
Before any of the techniques can be used, however, Dai must prove their safety. Skeptics, including Baker, say a nanotube’s shape could be problematic. Natural systems are rounded and soft, while nanotubes are rod-shaped and rigid. He envisions tubes lodging in the cell’s parts and jamming. Furthermore, when inhaled, the particles have elicited inflammatory responses in lungs. The carbon nanotubes will not break down, as will some more established nanomaterials used in medicine, such as nanopolymers.
Sticking is unlikely to be a problem, says Kevin Ausman, PhD, former director of operations at Rice University’s Center for Biological and Environmental Nanotechnology. Now at Oklahoma State University in Stillwater, he studies the health and environmental impacts of nanomaterials. Nano-tubes are actually quite flexible, on the scale of a molecule, he says. Tests show carbon nanotubes exhibit very low toxicity to cells. The walls might absorb other, non-target proteins such as albumins, another likely innocuous side effect. The public fears nanoparticles, such as carbon nanotubes, simply because they are small and new, he says.
Committed to using carbon nanotubes in medicine, Dai is cutting through the speculation by injecting mice with much higher doses than would likely ever be used in therapy. Carbon nanotubes seem to hold little danger, he says. They are composed of carbon, the fundamental element of life. When used in the body, carbon nanotubes are coated with biological molecules to increase their compatibility and eliminate clumping. Proteins linked to the tubes are bound so tightly they are unlikely to dislodge and get into trouble.
Many more tests must be conducted before the carbon nanotubes are ever used in humans. The technology is at least five years down the line, Dai estimates. While critics and advocates argue over the safety, he points to the mice he and his collaborators tested. They seem perfectly healthy and are able to eliminate at least some of the nanotubes from their bodies. Dai has found nanotubes in their urine and feces, but not enough to account for the total number injected into the mice. “We don’t know what happens to the rest, and what things they may do to the body,” he says, “but I think over time, they will come out.”
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