Photodynamic Molecular Beacon Triggered by Fibroblast Activation Protein on Cancer-Associated Fibroblasts for Diagnosis and Treatment of Epithelial Cancers

详细信息    查看全文

• 作者：Pui-Chi Lo ; Juan Chen ; Klara Stefflova ; Michael S. Warren ; Roya Navab ; Bizhan Bandarchi ; Stefanie Mullins ; Ming Tsao ; Jonathan D. Cheng ; Gang Zheng
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：January 22, 2009
• 年：2009
• 卷：52
• 期：2
• 页码：358-368
• 全文大小：514K
• 年卷期：v.52,no.2(January 22, 2009)
• ISSN：1520-4804

文摘

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.