Researcher Looks for More Targeted Way to Deliver Cancer Drugs

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The future of drug design lies in finding ways to target a drug specifically to a diseased cell, or even a molecule within that cell, while leaving healthy cells and molecules unharmed.

Victor Yang, professor of pharmacy at the University of Michigan, is using natural biomolecules to deliver medication in two parts, making it more Specifically lethal to select cells.

Yang recently received a $1.28 million, five-year grant from the National Institutes of Health to study cancer drug delivery.

Yang said researchers face multiple challenges in developing new treatments for cancer, including a lack of selectivity in the cells the drugs kill and difficulty getting through the cell membrane. They can add a target to the drug and tell it to go to the liver, for example, but that doesn’t solve the challenge of getting into the diseased cells and leaving healthy cells alone.

Yang’s approach is to give the patient an inactive drug that zeros in on the target cells, and then to inject a separate compound that tells the drug to activate only when it reaches its target. His method can also be used to create more precise images of diseased tissue.

He is using a combination of amino acids called the TAT peptide as a carrier molecule. This positively charged molecule normally carries a protein toward the cell’s membrane, which has a negative charge. Yang gives it a drug or activating compound to carry instead, and the peptide gets these molecules into the interior of the targeted cells---first the drug, and then the compound that turns it on.

The process works in experiments, though Yang said scientists are still unclear on how the peptide can get into the cell. He speculates that it may use the same tricks a virus does to invade a cell.

Yang would like to use a targeted approach on brain cancer because there is a nearly impervious membrane called the blood-brain barrier that prevents doctors from being able to directly get at brain tumors via the bloodstream with conventional medications. Traditional drugs tend to be molecules too large to cross the barrier. Targeting these cells with the TAT peptide carrier might allow doctors to image a tumor more precisely and find out how big it is while simultaneously delivering a therapeutic dose of medicine.

Yang’s work on the targeted drug delivery system is connected to his research on new ways to neutralize the anticoagulant Heparin. When Heparin is used in surgery to thin the patient’s blood, doctors later reverse the process with an antidote, and Yang has looked at using a fragment of a protamine molecule to do the job.

Yang is exploring ways that the same protamine segment might effectively penetrate the brain without harming healthy cells.

His aim is to arrive at a treatment that combines both the targeting and the drug therapy in one delivery system.

In addition to working on cancer drug deliver, Yang also has NIH grants to study treatment for peptic ulcers, Parkinson’s disease and blood clots.

In 2005, Yang was appointed by the Ministry of Education of China to receive a prestigious Cheung Kong Scholar Award, through which he has established his own laboratory at the School of Chemical Engineering at Tianjin University.

For more on Yang, visit: http://sitemaker.umich.edu/victoryang

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