Nanotubes destroy kidney tumors

By injecting multiwalled carbon nanotubes (MWCNTs) into tumors and heating them with a quick, 30-second zap of a laser, a multi-institutional team of researchers from the Wake Forest University School of Medicine (WFUSOM), Wake Forest University Center for Nanotechnology and Molecular Materials, Rice University, and Virginia Polytechnic Institute and State University has developed a new type of therapy that effectively kills kidney tumors in nearly 80% of treated mice. Researchers say that the findings, which were published in the Proceedings of the National Academy of Sciences of the United States of America, suggest a potential future cancer treatment for humans.

"When dealing with cancer, survival is the endpoint that you are searching for," said Suzy V. Torti, Ph.D., of WFUSOM and the study's lead investigator. "It's great if you can get the tumor to shrink, but the gold standard is to make the tumor shrink or disappear and not come back. It appears that we've found a way to do that."

Nanotubes are long, thin, nanoscale tubes made of carbon. For the study, researchers used MWCNTs, which contain several nanotubes nested within each other. The tubes, when noninvasively exposed to laser-generated, near-infrared radiation, respond by vibrating, thus creating heat. If enough heat is conducted, tumor cells near the tubes begin to shrink and die.

Using a mouse model, the researchers injected kidney tumors with different quantities of MWCNTs and exposed the area to a 3-watt laser for 30 seconds. They found that the mice that received no treatment for their tumors died about 30 days into the study. Mice that received the nanotubes alone or laser treatment alone survived for a similar length of time. However, in the mice that received the MWCNTs followed by a 30-second laser treatment, the higher the quantity of nanotubes injected, the longer the mice lived and the less tumor regrowth was seen. In fact, in the group that received the highest dose of MWCNTs, tumors completely disappeared in 80% of the mice. Many of those mice continued to live tumor free through the completion of the study, about 9 months later.

"You can actually watch the tumors shrinking until, one day, they are gone," Dr. Torti said. "Not only did the mice survive, but also they maintained their weight, did not have any noticeable behavioral abnormalities, and experienced no obvious problems with internal tissues. As far as we can tell, other than a transient burn on the skin that did not seem to affect the animals and eventually went away, there were no real downsides-that is very encouraging."

Current thermal ablation, or heat therapy, treatments for human tumors include radiofrequency ablation, which applies a single-point source of heat to the tumor rather than evenly heating the tumor throughout, such as with the MWCNTs described above. In addition to the MWCNTs used in this study, other nanomaterials, such as single-walled carbon nanotubes and gold nanoshells, are also currently undergoing experimental investigation as cancer therapies at other institutions.

"MWCNTs are more effective at producing heat than other investigational nanomaterials," Dr. Torti said. "Because this is a heat therapy rather than a biological therapy, the treatment works on all tumor types if you get them hot enough. We are hopeful that we will be able to translate this to humans."

In a separate study, William H. Gmeiner, Ph.D., WFUSOM, and his colleagues demonstrated that encasing MWCNTs in DNA increases the amount of heat generated upon irradiation. This study showed that DNA-encasement resulted in a threefold reduction in the concentration of MWCNTs needed to produce a temperature increase of 10 ˚C, enough of a rise to kill tumor cells. The investigators then demonstrated that a single pulse of laser irradiation following injection of the nanotubes into tumors completely eliminated the tumors in all the treated mice. Neither the treatment nor the irradiation affected surrounding healthy tissue.

The study using nanotubes to treat kidney tumors, which was funded by the National Cancer Institute, is detailed in the paper "Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation." An abstract is available at the journal's Web site.
View abstract

The study designed to increase the effectiveness of carbon nanotubes, which was funded in part by the National Cancer Institute, is detailed in the paper "Increased heating efficiency and selective thermal ablation of malignant tissue with DNA-encased multiwalled carbon nanotubes." An abstract is available at the journal's Web site.
View abstract

http://nano.cancer.gov