MIT engineers anti-cancer 'bomb'

MIT researchers claim to have designed a nanoparticle cancer drug 'that can burrow into a tumour, seal the exits and detonate a lethal dose of anti-cancer toxins, while leaving healthy cells unscathed'.

The dual-chamber, double-acting, drug-packing 'nanocell' proved effective and safe, with prolonged survival, against two distinct forms of cancer in mice, melanoma and Lewis lung cancer, shrinking the tumour, stopping angiogenesis and avoiding systemic toxicity 'much better than other treatment and delivery variations'.

'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 fundamental challenges in cancer chemotherapy are its toxicity to healthy cells and drug resistance by cancer cells, so cancer researchers were excited about anti-angiogenesis.' Anti-angiogenesis is the theory that cutting off the blood supply can starve tumors to death; however, this method can backfire as it also starves tumour cells of oxygen, prompting them to create new blood vessels, which can in turn instigate metastasis and other self-survival activities.

Another solution would be combining chemotherapy and anti-angiogenesis, but combination therapy has confronted an inherent engineering problem: 'you can't deliver chemotherapy to tumours if you have destroyed the vessels that take it there,' said Sasisekharan. Furthermore, the two drugs behave differently and are delivered on different schedules: anti-angiogenics over a prolonged period and chemotherapy in cycles.

To counter this problem, the MIT team used ready-made drugs and materials, to create 'a balloon within a balloon, resembling an actual cell'. They then 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 200nm size enables them to be 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, its outer membrane disintegrates, rapidly deploying the anti-angiogenic drug. This causes the collapse of the blood vessels feeding the tumour, thus trapping the loaded nanoparticle in the tumor, where it can slowly release the chemotherapy.

80% of the nanocell mice survived beyond 65 days, while mice treated with the best current therapy survived 30 days. Untreated animals died at 20.