Aug. 11, 2005 — Traditional attempts to destroy cancerous tumors involve treatments such as chemotherapy that kill healthy cells right along with mutated ones, often leaving patients weak, nauseous, hairless and vulnerable to infection.

But now biologists and engineers at the Massachusetts Institute of Technology have engineered a dual-chamber molecular bomb designed to infiltrate a tumor, shut down its blood vessels — thereby sealing off the exits — and detonate a dose of cancer-killing toxins.

The drug-delivering nanocell, reported recently in the journal Nature, could help usher in more effective cancer therapies that pinpoint and obliterate disease without harming normal, healthy cells.

"By having such a focused approach you are able to overcome these side effects," said team leader Ram Sasisekharan, professor of biological engineering at MIT.

Current-day medicine is trying to move toward an integrated approach that combines drugs designed to shut down the tumor's vascular network with treatments that work to destroy the cells.

But using these drugs in tandem presents some hurdles. If doctors obliterate a tumor's blood vessels, they also destroy the channels necessary to supply chemotherapeutic agents to the diseased tissue.

What's more, tumors often react to the vascular assault by going into a stage of hyperactive blood vessel production, challenging the therapy.

The nanocell promises to overcome these obstacles.

Engineered as a bubble within a bubble, the molecule's outer shell is designed to look like a fat cell, helping it to evade the body's immune system, which might otherwise recognize it as a foreign object and attack it.

The nanocell is also engineered to be small enough — about 200 nanometers in diameter — to slip into the porous environment of the tumor but too large to fit through the narrow blood vessels used as exits.

Once inside, the outer shell automatically releases a drug that begins to destroy the tumor's blood vessels in as little as 12 hours leading to a vascular shut down.

After about 30 hours, the outer shell falls away completely, exposing the inner bubble, which is broken down by enzymes naturally present in the tumor. As it does, it delivers its package of chemotherapy, a drug designed to slowly ooze into the cancer over a period of 15 days.

"The goal here is to get maximum killing while using minimum amounts of drug," said Samir Mitragotri, an associate professor at the University of California, Santa Barbara and expert in drug delivery techniques.

In lab experiments, the team was able to extend of lives of mice exhibiting melanoma or lung cancer to 65 days. Under the best known treatments such mice typically only survive 28 days.

Making the drug work in humans will take a few more years of research, though.

Sasisekharan and his team are now working with clinicians and the FDA to develop more advanced tests.