"One of the longstanding problems in medicine is how to cure cancer without harming normal body tissue," says Hongjie Dai, an associate professor of chemistry at Stanford and co-author of the study. "Standard chemotherapy destroys cancer cells and normal cells alike. That's why patients often lose their hair and suffer numerous other side effects. For us, the Holy Grail would be finding a way to selectively kill cancer cells and not damage healthy ones."
For the PNAS experiment, Dai and his colleagues used a basic tool of nanotechnology--carbon nanotubes, synthetic rods that are only half the width of a DNA molecule. Thousands of nanotubes could easily fit inside a typical cell.
"An interesting property of carbon nanotubes is that they absorb near-infrared light waves, which are slightly longer than visible rays of light and pass harmlessly through our cells," Dai says. But shine a beam of near-infrared light on a carbon nanotube, and the results are dramatic. Electrons in the nanotube become excited and begin releasing excess energy in the form of heat.
In the experiment, Stanford researchers found that if they placed a solution of carbon nanotubes under a near-infrared laser beam, the solution would heat up to about 158 degrees F (70 C) in two minutes. When nanotubes were placed inside cells and radiated by the laser beam, the cells were quickly destroyed by the heat. However, cells without nanotubes showed no effects when placed under near-infrared light.
"It's actually quite simple and amazing," Dai observes. "We're using an intrinsic property of nanotubes to develop a weapon that kills cancer."
To assure that only diseased cells were destroyed in the experiment, the scientists had to find a way to selectively deliver carbon nanotubes into cancer cells and not into healthy ones. Dai and his co-workers achieved this by performing a bit of biochemical trickery. Unlike normal cells, the surface of a cancer cell contains numerous receptors for a vitamin known as folate. The researchers decided to coat the nanotubes with folate molecules, which would only be attracted to diseased cells with folate receptors.
The experiment worked as predicted. Most of the folate-coated nanotubes ended up inside cancer cells, bypassing the normal cells--like Trojan horses crossing the enemy line. Once the nanotubes were planted inside, the researchers shined the near-infrared laser on the cancer cells, which soon heated up and died.
"Folate is just an experimental model that we used," Dai says. "In reality, there are more interesting ways we can do this. For example, we can attach an antibody to a carbon nanotube to target a particular kind of cancer cell."
One example is lymphoma, or cancer of the lymphatic system. Like many cancers, lymphoma cells have well-defined surface receptors that recognize unique antibodies. When attached to a carbon nanotube, the antibody would play the role of a Trojan horse. Dai and Dean Felsher, a lymphoma researcher in the Stanford School of Medicine, have begun a collaboration using laboratory mice with lymphoma. The researchers want to determine if shining near-infrared light on the animal's skin will destroy lymphatic tumors, while leaving normal cells intact.
"It's a really interesting idea," says Felsher, an assistant professor of medicine and of pathology. "For a long time people have thought about ways to target cancer cells, and this is a very promising technique."
Researchers at Rice University recently conducted a similar experiment on mice with cancerous tumors. Instead of carbon nanotubes, t he Rice team injected the tumors with gold-coated nanoshells and exposed the animals to near-infrared light for several minutes. The tumors disappeared within 10 days without damaging any healthy tissue.
Dai points out that the carbon nanotubes also can be delivered to diseased cells by direct injection. "In breast cancer, for example, there might come a time when we inject nanotubes into the tumor and expose the breast to near-infrared light," he says. This benign therapy could potentially eliminate months of debilitating chemotherapy and radiation treatment, he adds.
"The laser we used is a 3-centimeter beam that's held like a flashlight," he notes. "We can take the beam and put anywhere we want. We can shine it on a local area of the skin or inside an internal organ using a fiber-optic device."
Dai has applied for a patent on the procedure through Stanford's Office of Technology Licensing (OTL). He also has patented another technique that uses pulses of near-infrared light to shake the DNA molecule loose from the carbon nanotube after they've entered the cell. The idea is to use the nanotube to deliver therapeutic molecules of DNA, RNA or protein directly into the cell nucleus to fight various infections and diseases.
"Nanotechnology has long been known for its applications in electronics," Dai concludes. "But this experiment is a wonderful example of nanobiotechnology--using the unique properties of nanomaterials to advance biology and medicine."
Dai's graduate student, Nadine Wong Shi Kam, is lead author of the PNAS study. Other co-authors are Michael O'Connell, a former postdoctoral fellow in the Department of Chemistry, and graduate student Jeffrey A. Wisdom in the Department of Applied Physics.
The study was partly supported by the National Science Foundation Center on Polymer Interfaces and Macromolecular Assemblies, a research partnership among Stanford, IBM Almaden Research Center , University of California-Davis and University of California-Berkeley.