Brass Knuckles for Cancer Drugs

Brass knuckles

Any good brawler knows that the power of a punch depends both on his muscle and the extra heft he attaches to his mitt.

Similarly, engineers and medical-center researchers have discovered that by adding a "macromolecular weight" to cancer chemotherapy drugs, they can make the drugs penetrate and accumulate inside tumors more effectively. Without the ballast, the drugs often fail to deliver their full impact because they diffuse in and out of the tumor too rapidly.

In an article in the Journal of the National Cancer Institute, Ashutosh Chilkoti, associate professor of biomedical engineering, and his colleagues described how they had tested a molecule called dextran as a molecular weight on cancer drugs. Dextran is a harmless chain of sugar molecules.

The heavier molecule performs better because tumor vessels are leakier than normal vessels and thus more likely to absorb the enhanced drug molecule. Because the molecules cannot as easily permeate normal blood vessels, toxicity to healthy tissues is reduced.

"Small molecules penetrate the tumor very efficiently, but are also removed very efficiently," Chilkoti says. "Larger molecules penetrate more slowly, but they stay in the tissue longer, giving the patient a greater concentration of the drug. If you balance the two factors with a precise weight, you get optimal drug concentration."

Of additional benefit, macromolecular drug carriers can be substituted for the toxic substances routinely mixed with chemotherapy to make it more soluble. Macromolecular molecules can selectively carry the drug to the tumor simply because of their size and do not need such noxious carriers, says Chilkoti.

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