down and processed, releasing the drug.

One of the key mechanisms of this breakdown is disulfide reduction, which involves the breaking of chemical bonds. It was thought that disulfide reduction relied on the movement of the material along microtubules, hollow tube like structures, and fusion with special digestive-enzyme containing compartments within the cell called lysosomes. However, the research showed that disulfide reduction occurred even when such components were removed from the process.

By inactivating different cellular components, Yang discovered which components are essential to the disulfide reduction process.

"It was surprising to learn that many other components of the cell, aside from those previously assumed to be responsible, were capable of releasing the drug from folic acid," Yang said. "This significantly increases the opportunity for the drug to be released. For instance, we used to believe it had to get to a specific location to be released, and now we know it can happen almost anywhere during endocytosis."

The mechanisms, locations and cellular components involved in the release of drugs within a cell had been under debate for several years, Low said.

"This is the definitive statement on how drugs are released within a cell," he said. "We will use this knowledge to develop better receptor-targeted drug therapies to treat cancer and other diseases."

Low and Yang worked with scientists from the Department of Chemistry, Weldon School of Biomedical Engineering and Endocyte, and used facilities at the Oncological Sciences Centre, part of the Purdue Cancer Centre, and Bindley Bioscience Centre at Purdue's Discovery Park.

Endocyte Inc. develops receptor-targeted therapeutics for the treatment of cancer and autoimmune diseases. Endocyte has three compounds in Food and Drug Administration-regulated clinical trials: EC20, a targeted diagnostic agent that is in Phase I
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