THE BATTLE against cancer has entered a new phase and if Ram Sasisekharan and his team's work proves to be efficacious in humans, treating some forms of cancer is likely to become effective, safe and truly path breaking.

While they have essentially used the existing methods of treating cancer, what is truly innovative is the way they have used them for achieving the same.

Dr. Sasisekharan who is a professor in the Biological Engineering Division at Massachusetts Institute of Technology, U.S., has turned to nanotechnology to achieve promising results in animal models. The results were published in the July 28 issue of the journal Nature.

Conventional methods

While conventional chemotherapy treatment is effective in treating cancer, it has its own share of problems — inability to target just the cancer cells and the possibility of cancer cells developing drug resistance.

Cells, be they normal or cancerous, depend on blood supply for sustenance and oxygen. Cutting off blood supply could be one way to kill the cancer cells.

This is however fraught with problems as cancer cells have a propensity to create new blood vessels. The process of cutting off blood supply is called anti-angiogenesis. Combining the two methods — chemotherapy and anti-angiogenesis — can be another way to kill cancer cells. This has it own limitations though — drugs that cut off blood supply not only deprive cancer cells of oxygen but also chemotherapy drugs that can kill the cancer cells.

Two-in-one

Dr. Sasisekharan used the above combination, but in a different way — `nanocells' (of 200 nanometres in size) in a balloon within a balloon design — to deliver chemotherapy agents and drugs for destroying the blood supply to the cancer cells. The outer balloon has the anti-angiogenesis agent and the inner balloon has chemotherapy drugs.

"We tried the other combination but it will not work out," Dr. Sasisekharan explained. "First you need a vascular shut down (blood supply cut off) and then release the chemotherapy drug.

"This will not only increase the therapeutic index but also decrease the toxicity. And this will happen only if the outer balloon is filled with an anti-angiogenesis drug."

The ability of the `nanocells' to wreak complete destruction of cancerous cells is aided by the cancerous cells themselves. "Tumour vessels suck things into their environment and the nanocells get trapped in the tumour bed due to their large size," he elucidated.

The size of the nanocell plays a crucial role. While the 200 nanometre size of the nanocell prevents it from coming out of the blood vessel into organs, at the site of tumour it is a different story.

Leaky vessels

"Here the blood vessels are leaky and have pores as large as 400-600 nanometres," he noted. "So the nanocells can pass through the vessels into the tumour where they are retained."

In other words Dr. Sasisekharan and his team used the difference in pathology of blood vessels in the tumour and the normal organs to selectively deliver the drugs.

Once inside the tumour, the nanocell's outer balloon disintegrates and the anti-angiogenesis drug brings about the blood vessel collapse, shrinkage and shut down.

The chemotherapy drugs in the inner balloon are then released slowly as prolonged exposure of the tumour to chemotherapy has greater efficacy in killing cancer cells.

"It may not be optimal to release the anti-angiogenesis and chemotherapy drugs simultaneously as the chemotherapeutic drugs may leak out before the blood vessels inside the tumour are cut," he elucidated.

"If both drugs are released simultaneously, it becomes a simple combination therapy and though such a combination did show some efficacy (in our study), the nanocell was far superior to such a combination."

Selection of drugs

The team had worked on animal models to treat melanoma and Lewis lung cancer. "There is no universal chemotherapeutic agent — they are dependent on the cancer," he observed. "We need to find the right combination of drugs that will work for a given tumour."

Eighty per cent of mice treated with nanocells survived beyond 65 days compared with 30 days in the case of mice treated with the best current therapy. "The 65-day period wasn't a benchmark," he noted. "When we started this study, we did not expect the animals to survive this long."

R. PRASAD

in Chennai

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