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Study Findings Could Help In Developing A Better Drug Delivery System

arly illuminating the process," Yang said. "This is the first optical method to be developed to monitor this release. The main promise of this method is that it does not damage the cells being studied. Therefore, we are able to observe the process under true physiological conditions and watch it right as it is happening."

This research, funded by Endocyte, will be detailed in a paper in Tuesday's (Sept. 12) issue of the Proceedings of the National Academy of Sciences and is currently available online.

In targeted drug therapy, drugs are linked to molecules that are used in excess by pathologic cells, for example a required nutrient, in order to transport drugs directly to the targeted cells while avoiding significant delivery of the toxic drug to normal cells. A commonly used agent, referred to as a ligand, is the vitamin folic acid. Cancer cells need folic acid to grow and divide and, therefore, have developed abundant receptors to capture it. These receptors are largely absent in normal cells. This means folic acid, and the drug linked to it, is attracted to the pathologic cells and is harmless to healthy cells, Low said.

Low led the team that discovered this folate-targeted treatment method in 1991 and the receptor-targeted technology is proprietary to Endocyte.

"It is desirable to have the drug released from the ligand, folic acid, once the folate-linked complex enters the cell," Yang said. "This 'conditional drug release' is usually realized by attaching folate to the drug through a linker that falls apart inside the cell. There were several linkers in common use, but with mixed efficiency. In this study we undertook to interrogate the full details of this breakdown process."

Yang examined receptor endocytosis, the process by which cells absorb materials — such as a drug attached to folic acid — that have been captured at special sites, called receptors, on the cell surface. The compound is then broken
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