Nano-Trojan horse for cancer

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PostPosted: Mon Oct 23, 2006 11:08 am    Post subject: Nano-Trojan horse for cancer Reply with quote

A nano-Trojan horse for cancer
Tiny fat blobs are used to move protein-killing RNA into sick cells

Medical scientists have great power in their laboratories, and perhaps nowhere more so than with a technique known as RNA interference.

By harnessing the potential of short bits of RNA inside cells, researchers have gained the power to shut off a gene's capability to make proteins. Emerging in the last decade, this ability to "silence" genes holds great promise for treating human diseases by stopping the production of harmful proteins.

The tiny bits of RNA work well in cells, but getting them into human cells within the body has proved more problematic. That's because the body's defense mechanisms perceive the RNA bits as invaders and kill them before they can reach their intended target.

Now, a team led by Dr. Anil Sood, an associate professor at the University of Texas M.D. Anderson Cancer Center, may have solved the problem for ovarian cancer, opening the door to promising treatments for other forms of cancer.

"The purpose of our research was to figure out how to get these short pieces of RNA into tumor cells," Sood said.

Sood's first step was to identify bits of RNA with considerable cancer-killing promise. In lab dishes, the selected RNA shut down production of a protein that helps ovarian cancer cells survive and spread.

Difficult to penetrate
Most cancer drugs target proteins on the exterior walls of cells because cells are so difficult to penetrate. For Sood's RNA drug to work, it had to find a doorway into the cells to get at the targeted protein.

After studying different capsules to ferry their drug inside the body, Sood's team settled upon liposomes, or tiny balls of fat. They are only 60 to 125 nanometers across, about one-millionth of an inch.

The size is important because the liposomes are small enough to fit into blood vessels leading to tumor cells but too big to get through the narrower vessels leading to healthy cells.

"This particle is so small, it has no problem getting through the tumor's vasculature and into the tumor," said Dr. Gabriel Lopez-Berestein, one of Sood's collaborators at M.D. Anderson.

Sood's group then developed a straightforward way to implant RNA within the liposomes, which acts as a protective sheath during the voyage through the body.

So, what happened when they tried their concoction on mice infected with ovarian cancer?

Death and destruction for the cancer cells. A group of mice that received the RNA/liposome injections saw the average weight of their tumors reduced by 44 percent to 72 percent, compared with control groups. When the injections were combined with a standard chemotherapy drug for ovarian cancer, the average tumor weights were reduced by 94 percent to 98 percent.

Toxicity testing
Although there is no certainty those results will hold true in humans, the research represents a novel mechanism for transporting bits of RNA inside the body to desirable targets. The work was published earlier this month as the lead article in the journal Clinical Cancer Research.

Now, the research group is studying the RNA/liposome drug's toxicity in human blood. So far, the results have been encouraging, with it appearing to cause no harm to blood cells and platelets.

Sood said he is in discussion with the U.S. Food and Drug Administration to begin formal toxicity studies within the next year, and he hopes to start human clinical trials in less than two years.

The therapy also has potential beyond ovarian cancer. The protein targeted by Sood's drug is produced in excessive amounts by colon, breast, thyroid, and head and neck cancers.


This story was first posted on 28th August 2006.
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