The team 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 tumor. They are small enough to pass through tumor vessels, but too large for the pores of normal vessels.
Once the nanocell is inside the tumor, its outer membrane disintegrates, rapidly deploying the anti-angiogenic drug. The blood vessels feeding the tumor then collapse, trapping the loaded nanoparticle in the tumor, where it slowly releases the chemotherapy.
The team tested this model in mice. The double-loaded nanocell shrank the tumor, stopped angiogenesis and avoided systemic toxicity much better than other treatment and delivery variations.
But it is patient survival and quality of life that really inspire this research, Sasisekharan said. Eighty percent of the nanocell mice survived beyond 65 days, while mice treated with the best current therapy survived 30 days. Untreated animals died at 20.
"It's an elegant technique for attacking the two compartments of a tumor, its vascular system and the cancer cells," said Judah Folkman of Children's Hospital Boston. "This is a very neat approach to drug delivery," said MIT Institute Professor Robert Langer.
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," says Sasisekharan. "It's not going to stop here. We want to build on this concept."