Evaluation of efficient intracellular release of anticancer agents from tumor-targeting delivery system

MEDI 74

Shuyi Chen, shcchen@ic.sunysb.edu1, Xianrui Zhao, xizhao@ic.sunysb.edu1, Jin Chen, jinchen2@ic.sunysb.edu1, and Iwao Ojima, iojima@notes.cc.sunysb.edu2. (1) Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, (2) Department of Chemistry and ICB&DD, State University of New York at Stony Brook, The Chemistry Bldg, Stony Brook, NY 11794-3400
A novel disulfide-containing linker for tumor-targeting prodrug has been designed and synthesized. This bifunctional linker which contains a carboxylic acid group and an active ester terminus can be used as general model for tumor-targeting drug delivery. A series of model experiments have been performed and proved the designed release mechanism, i.e., disulfide bond cleavage by a thiol, fast intramolecular thiolactonization, and the release of a free cytotoxic agent. To further investigate the endocytosis and drug release mechanism, several fluorescent and fluorogenic compounds, in which biotin or DHA acts as targeting moiety, have been also synthesized. Their application to the study on the internalization and intracellular drug release will be presented.

 

General Poster Session
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006