"We brought together three elements: cancer biology, pharmacology and engineering," said Ram Sasisekharan, a professor in MIT's Biological Engineering Division and leader of the research team. The dual-chamber, double-acting, drug-packing "nanocell" proved effective and safe, with prolonged survival, against two distinct forms of cancers - melanoma and Lewis lung cancer - in mice.
Using ready-made drugs and materials, "we created a balloon within a balloon, resembling an actual cell," explains Shiladitya Sengupta, a postdoctoral associate in Sasisekharan's laboratory.
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 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 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.
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."
MEDICA.de; Source: Massachusetts Institute of Technology