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Lo PC , Chen J , Stefflova K , Warren MS , Navab R , Bandarchi B , Mullins S , Tsao M , Cheng JD , Zheng G
Photodynamic Molecular Beacon Triggered by Fibroblast Activation Protein on Cancer-Associated Fibroblasts for Diagnosis and Treatment of Epithelial Cancers
Journal of Medicinal Chemistry. 2009 Jan;52(2) :358-368
PMCID: PMC2773291   
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Fibroblast activation protein (FAP) is a cell-surface serine protease highly expressed on cancer-associated fibroblasts of human epithelial carcinomas but not on normal fibroblasts, normal tissues, and cancer cells. We report herein a novel FAP-triggered photodynamic molecular beacon (FAP-PPB) comprising a fluorescent photosensitizer and a black hole quencher 3 linked by a peptide sequence (TSGPNQEQK) specific to FAR FAP-PPB was effectively cleaved by both human FAP and murine FAR By use of the HEK293 transfected cells (HEK-mFAP, FAP(+); HEK-vector, FAP(-)), systematic in vitro and in vivo experiments validated the FAP-specific activation of FAP-PPB in cancer cells and mouse xenografts, respectively. FAP-PPB was cleaved by FAP, allowing fluorescence restoration in FAP-expressing cells while leaving non-expressing FAP cells undetectable. Moreover, FAP-PPB showed FAP-specific photocytotoxicity toward HEK-mFAP cells whereas it was non-cytotoxic toward HEK-Vector cells. This study suggests that the FAP-PPB is a potentially useful tool for epithelial cancer detection and treatment.
Lo, Pui-Chi Chen, Juan Stefflova, Klara Warren, Michael S. Navab, Roya Bandarchi, Bizhan Mullins, Stefanie Tsao, Ming Cheng, Jonathan D. Zheng, Gang AMER CHEMICAL SOC 395KD