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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
J Med Chem. 2009 Jan 22;52(2) :358-68
PMID: 19093877    PMCID: PMC2773291    URL: https://www.ncbi.nlm.nih.gov/pubmed/19093877
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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 FAP. FAP-PPB was effectively cleaved by both human FAP and murine FAP. 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 eng K08 CA090468-05/CA/NCI NIH HHS/ P30 CA006927/CA/NCI NIH HHS/ P30 CA006927-47/CA/NCI NIH HHS/ Research Support, Non-U.S. Gov't J Med Chem. 2009 Jan 22;52(2):358-68. doi: 10.1021/jm801052f.