"The Big C" vs Tiny Weapons

Nanotechnology could revolutionize breast cancer treatment

These days, smaller is where it's at. Laptops have slimmed down and lightened up, phones and watches packed with technology can multi-task to beat the band, computer chips smaller than most adults' pinky nail are capable of storing the contents of thousands of books and personal listening devices can be had in postage stamp-size.

Nanoparticles are very small particles indeed. Experts at Dartmouth's Center of Cancer Nanotechnology Excellence, which received a five-year, $12.8 million grant from the National Cancer Institute, are conducting research with constructed nanoparticles that are "much smaller than a cell. You could put maybe a million of them into one cell," says P. Jack Hoopes, DVM, PhD, Professor of Surgery and Medicine at the Geisel School of Medicine at Dartmouth;adjunct professor of EWngineering at the Thayer School of Engineering; director of Surgery and Radiation Research Laboratories; and co-director of the NCCC Nanotechnology Working Group.

Nanotechnology offers multi-pronged appeal to experts in the biomedical field. First, nano-based materials can act as carriers that either deliver the nanomaterial itself or an attached substance to specific locations in the body, such as cancer cells. Dartmouth researchers, for instance, are exploring the idea of attaching antibodies to iron-oxide nanoparticles. The antibodies are a bit like puzzle pieces that will only fit cancer cells, so that the distribution of medicine in the body is restricted. In other words, nanoparticles will in effect act as biological mail carriers, transporting cell-destroying medicine to particular addresses – cancerous cells – while bypassing normal cells. "In all cancer therapy," Hoopes says, "it doesn't matter if it's radiation or chemotherapy or whatever, one of the biggest challenges and the main goal is to target the therapy" so that normal tissue is left unharmed. Nanotechnology appears to be capable of achieving that goal.

Nanotechnology could further reduce harmful aspects of cancer therapy by allowing physicians to opt for substances such as the iron oxide that Dartmouth researchers have chosen. Based on the Dartmouth model, a doctor would inject cancer patients with the iron-oxide nanoparticles and attached antibodies, and then activate the nanoparticles with a magnetic field similar to that of an MRI. The magnetic field would generate heat within the nanoparticles, killing the cancer cells. But of important note is the fact that the magnetic field by itself is nontoxic, and iron oxide, unless taken in vast quantities or activated by the magnetic field, is also nontoxic, Hoopes says.

In contrast, the traditional cancer treatment mainstays of chemotherapy and radiation "are really toxic, and they have to be toxic. If they weren't toxic, they wouldn't kill the cancer cells," Hoopes says. "And so, you're always walking this tightrope with therapy. [Patients] are given enough therapy to kill the cancer cells but not too much therapy because you want to spare the normal tissue, and that's a fine line. Radiation oncologists and therapy oncologists have to fight that battle every day." Since nontoxic nanoparticles would target and destroy only cancerous cells when the magnetic field heats things up, nanotechnology is viewed as a potential game-changer that could help patients avoid bouts of chemotherapy and radiation, which do not discriminate between normal and cancerous cells.

In addition, nanotechnology has the potential to provide doctors with a better way to treat the finger-like areas that extend outward from some tumors, as well as the varied locations of cancer within a patient. "Once tumors get beyond the primary stage and metastasize and appear in multiple sites, they become very difficult to treat with conventional therapies such as radiation and surgery," Hoopes says, especially when a tumor grows in a particularly sensitive area, such as the brain. Traditionally, treatment of the outgrowths of a tumor can require that a surgeon cut into an area that goes beyond the main body of the tumor. "But we can't always cut it all out because we can't afford to give up all the tissue that's around the tumor," Hoopes says. Nanotechnology, with its ability to effectively distinguish between good and bad cells, could provide a solution to this quandary by enabling doctors to deliver nanoparticles in a systemic way to patients, resulting in safer and more effective treatment of tumors that have spread beyond a primary tumor – even cancerous areas so small that they don't show up through imaging such as an MRI, Hoopes says.

The future might not be that far off

Dartmouth researchers have already tested their nanotechnology-based cancer treatment on mice and have treated two dogs (local pets that live in New Hampshire and Vermont) that had tumors. The dogs were selected for the procedure because they had tumors of the mouth, allowing Hoopes to clearly monitor the response to treatment. The results? "Both dogs are doing well so far," he says. "They're fine."

Nanotechnology appears to be "where the whole [cancer] field is going in the next 20 years," Hoopes says. It could hold the key to designing therapies that are specialized and able to identify individual cancer cells, and it is already being applied to human patients in initial clinical trials in United States' locations, including Houston and Boston.

And, although Dartmouth experts are focusing their iron-oxide nanotechnology research on breast cancer, nanotechnology-based treatments could apply to other diseases and types of cancer, as well, Hoopes says. In fact, the nanotechnology studies have potential applications for any kind of medicine in which a doctor wants to target the delivery of medicine, he says. NH