MIT engineers anti-cancer smart bomb
tumour, cut off its blood supply and release a lethal dose of
anti-cancer toxins, while leaving healthy cells unscathed.
The idea of using nanoparticles as a therapeutic 'Trojan horse', attacking the cancer cell by stealth from within, is entirely new, and demonstrates the possibilities nanotechnology has, especially in drug and therapeutic applications.
The double-acting, drug-packing nanocell, leaves healthy cells unscathed, against two distinct forms of cancers - melanoma and lung cancer - in mice.
The team, from the Massachusetts Institute of Technology (MIT), loaded the outer membrane of the nanocell with an anti-angiogenic drug and the inner balloon with chemotherapy agents.
A "stealth" surface chemistry allows the nanocells to evade the immune system, while their size (200 nanometers) makes them preferentially taken into the tumour. They are small enough to pass through tumour vessels, but too large for the pores of normal vessels.
Once the nanocell is inside the tumour, its outer membrane disintegrates, rapidly deploying the anti-angiogenic drug. The blood vessels feeding the tumour then collapse, trapping the loaded nanoparticle in the tumour, where it slowly releases the chemotherapy.
The team tested this model in mice. The double-loaded nanocell shrank the tumour, stopped angiogenesis and avoided systemic toxicity much better than other treatment and delivery variations.
Eighty per cent of the nanocell mice survived beyond 65 days, while mice treated with the best current therapy survived 30 days. Untreated animals died at 20.
The nanocell worked better against melanoma than lung cancer, indicating the need to tweak the design for different cancers. "This model enables us to rationally and systematically evaluate drug combinations and loading mechanisms," said Ram Sasisekharan, a professor in MIT's Biological Engineering Division and leader of the research team.
"It's not going to stop here. We want to build on this concept."
Until recently researchers were faced with the problem that cutting the blood vessels removed the means of delivering the anti-cancer drugs.
"The fundamental challenges in cancer chemotherapy are its toxicity to healthy cells and drug resistance by cancer cells," Sasisekharan said.
"So cancer researchers were excited about anti-angiogenesis. The theory that cutting off the blood supply can starve tumors to death. That strategy can backfire, however, because it also starves tumour cells of oxygen, prompting them to create new blood vessels and instigate metastasis and other self-survival activities," he added.
Sasisekharan said that the next step would be combining chemotherapy and anti-angiogenesis-dropping the bombs while cutting the supply lines. However, this approach comes with an inherent engineering problem.
"You can't deliver chemotherapy to tumours if you have destroyed the vessels that take it there," Sasisekharan said.
"Also, the two drugs behave differently and are delivered on different schedules: anti-angiogenics over a prolonged period and chemotherapy in cycles."
The work will be reported in the July 28 issue of Nature, with an accompanying commentary.
