Nanotechnology-based cancer therapy is advancing step-by-step toward human clinical trials. In a recent demonstration in rabbits, nanoparticles targeted to the growing blood vessels feeding tumors shrank the tumors using far less chemotherapy drug (and therefore with no harmful side effects) than would have been required to shrink the tumors if the drug had been used alone, without nanotech. Furthermore, targeting image-enhancing nanoparticles to the tumors showed a large reduction in the blood vessels surrounding the tumors. From “Nano-sized technology has super-sized effect on tumors“, a Washington University in St Louis news release written by Gwen Ericson:
Anyone facing chemotherapy would welcome an advance promising to dramatically reduce their dose of these often harsh drugs. Using nanotechnology, researchers at Washington University School of Medicine in St. Louis have taken a step closer to that goal.
A tumor treated with fumagillin nanoparticles (left) is smaller than an untreated tumor. Nanoparticles containing an image enhancing metal (yellow) show that the treated tumor has much less blood vessel growth than the untreated tumor.
The researchers focused a powerful drug directly on tumors in rabbits using drug-coated nanoparticles. They found that a drug dose 1,000 times lower than used previously for this purpose markedly slowed tumor growth.
“Many chemotherapeutic drugs have unwanted side effects, and we’ve shown that our nanoparticle technology has the potential to increase drug effectiveness and decrease drug dose to alleviate harmful side effects,” says lead author Patrick M. Winter, Ph.D., research assistant professor of medicine and biomedical engineering.
The nanoparticles are extremely tiny beads of an inert, oily compound that can be coated with a wide variety of active substances. In an article published online in The FASEB Journal (abstract), the researchers describe a significant reduction of tumor growth in rabbits that were treated with nanoparticles coated with a fungal toxin called fumagillin. Human clinical trials have shown that fumagillin can be an effective cancer treatment in combination with other anticancer drugs.
In addition to fumagillin, the nanoparticles’ surfaces held molecules designed to stick to proteins found primarily on the cells of growing blood vessels. So the nanoparticles latched on to sites of blood vessel proliferation and released their fumagillin load into blood vessel cells. Fumagillin blocks multiplication of blood vessel cells, so it inhibited tumors from expanding their blood supply and slowed their growth.
Human trials have also shown that fumagillin can have neurotoxic side effects at the high doses required when given by standard methods. But the fumagillin nanoparticles were effective in very low doses because they concentrate where tumors create new blood vessels. The rabbits that received fumagillin nanoparticles showed no adverse side effects.
…”What this report clearly demonstrates is that our nanoparticles can carry chemotherapeutic drugs specifically to tumors and have an effect at the tumor site,” [Senior author Gregory M.] Lanza says. “Sometimes when I give presentations about our nanotechnology, people react as if it was science fiction or at best a technology of the distant future. But we’ve shown that the technology is ready for medical applications now.”
The nanoparticles will be tested this year in preliminary human clinical trials to determine the optimal method for using them as imaging agents. These studies will lay essential groundwork for using the nanoparticles as therapeutic agents.
—Jim
