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Weighting cancer drugs to make them hit tumors harder

Scientists have devised a blueprint for boosting anti-cancer drugs' effectiveness and lowering their toxicity by attaching the equivalent of a lead sinker onto the drugs. This extra weight makes the drugs penetrate and accumulate inside tumors more effectively.

Chemotherapy drugs often fall short of achieving their full impact because the drugs diffuse in and out of the tumor too rapidly, said the scientists from Duke University Medical Center and Duke's Pratt School of Engineering.

The scientists increased the size of the drug by adding a "macromolecular weight" that increases its concentration and staying power inside the tumor. The heavier molecules are more selectively absorbed by tumors because tumor blood vessels are more permeable or "leakier" than normal blood vessels. Thus, larger molecules can pass through the tumor vessels more easily.

Drugs with a greater molecular weight also reduce chemotherapy's toxicity to healthy tissue because the large molecules cannot easily permeate normal blood vessels. As a result, normal tissue receives less of the drug than does the tumor.

Results of the study, funded by the National Institute of Biomedical Imaging and Bioengineering, a branch of the National Institutes of Health, are published in the March 1, 2006, issue of the Journal of the National Cancer Institute.

"Small molecules penetrate the tumor very efficiently, but are also removed very efficiently," said Ashutosh Chilkoti, Ph.D, a Duke biomedical engineer and senior author of the study. "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."

Chilkoti said current chemotherapy drugs are so small � molecular weight of 300 to 600 � that they are reabsorbed into the bloodstream before their anti-cancer effects are fully achieved.

Overcoming this
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-660-8414
Duke University
2-Mar-2006


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