An introductory talk from the director of the Center for Nanotechnology and Molecular Materials at Wake Forest University's (Winston-Salem, North Carolina) School of Medicine about the value of nanomaterials sparked an idea among researchers that may now lead to an effective kidney cancer cure.
Researchers there have just reported using nanotubes to eliminate cancerous kidney tumors and insure that they don't return. Nanotubes are injected into the tumors and heated with a laser to effectively kill tumors in nearly 80% of mice tested, suggesting a potential future cancer treatment for humans.
"Our lab is interested in relationships between iron and cancer," Suzy Torti, PhD, a professor of biochemistry at WFU School of Medicine, told Medical Device Daily. "We came to study nanotubes because of the proximity of the Nanotechnology Center. A talk by the director, David Carroll, got everybody here excited. These particles have some iron and that can be used as contrast agents and those were our initial thoughts, but it became clear that nanomaterials were useful for more than that."
The work, reported in the August issue of the Proceedings of the National Academy of Sciences (PNAS) reports how carbon-based multi-walled nanotubes (MWCNTs), which contain several nanotubes nested within each other, were injected into tumors and then zapped with a 30-second dose of near-infrared radiation.
Rather than delivering the nanotubes systemically, Torti's team injected them directly into tumors, so that "... they didn't have to find the tumors. That was a first step – just proof that they can be tumor-ablative agents if you can get them to the right place at the right time.
"Then we exposed it to a near infrared laser radiation," she said. "When you do that, nanotubes begin to vibrate pretty fast, creating heat. It's localized to where the infrared radiation hits the tubes causing death of tumor cells."
For the study, Torti's team reported that mice who received no treatment for their tumors died about 30 days into the study. Those that received the nanotubes alone or had laser treatment alone survived for a similar length of time. Tumors disappeared for 80% of mice that received the MWCNTs combined with laser treatment.
Nine months later, many of the treated mice remained tumor free.
"Nanotubes are pretty efficient at absorbing light ... a broad absorption spectrum relative to other materials," Torti said when asked why she chose nanotubes rather than another nanomaterial. "They can also absorb near-infrared radiation. They're pretty efficient at absorption and reduce the amount of laser light needed to excite them."
Torti and her colleagues chose to try the treatment on kidney tumors because, "People have tried radio frequency ablation, which is a similar idea. A tip is inserted into the kidney to generate heat. But there are shortcomings. Although ablation is successful, the probe is not the best; there is seeding of tumors along the tumor trace. Using MWCNTs plus near-infrared radiation provides more diffuse heating."
Thermal ablation treatments for human tumors currently include radio frequency ablation, which applies a single-point source of heat to the tumor rather than evenly heating the tumor throughout, like the MWCNTs can do.
Torti said her team was able to watch the tumors shrink, day by day, until they disappeared.
"Not only did the mice survive, but they maintained their weight, didn't have any noticeable behavioral abnormalities and experienced no obvious problems with internal tissues," she said. "As far as we can tell, other than a transient burn on the skin that didn't seem to affect the animals and eventually went away, there were no real downsides – that's very encouraging."
Torti's team noted the thermal effects generated by MWCNTs had added benefits, beyond the ablation of cancerous tumors. "For example, hyperthermia can increase the permeability of tumor vasculature, which can enhance the delivery of drugs into tumors, as well as synergistically enhance tumor cytotoxicity when combined with chemotherapy or radiotherapy," according to the PNAS article.
The next step is to explore systemic delivery and use a "slightly less contrived system" so that kidney tumors are actually resident in the kidney, rather than a subcutaneous placement as was the case for this study, in order to move closer to clinical applications.
The team will then begin toxicology and pharmacology studies. It's unknown what happens to the nanotubes after they are used. Torti said she observed (anecdotally, but not reported) that a certain number do remain at the site. It's not a bad thing, she said, because it provides an opportunity for retreatment with additional zaps of radiation if necessary.
A grant from the National Cancer Institute (Bethesda, Maryland) and a private donation will keep the wheels turning on this research project for several more years. Torti estimates that it would take at least "a few more years" of work to test the new therapy before human trials could begin, "even if everything worked remarkably well."