Photodynamic molecular beacon triggered by fibroblast activation protein on cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Juan Chen
  • Klara Stefflova
  • Michael S. Warren
  • Roya Navab
  • Bizhan Bandarchi
  • Stefanie Mullins
  • Ming Tsao
  • Jonathan D. Cheng
  • Gang Zheng

Detail(s)

Original languageEnglish
Pages (from-to)358-368
Journal / PublicationJournal of Medicinal Chemistry
Volume52
Issue number2
Publication statusPublished - 22 Jan 2009
Externally publishedYes

Abstract

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. © 2009 American Chemical Society.

Citation Format(s)

Photodynamic molecular beacon triggered by fibroblast activation protein on cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers. / Lo, Pui-Chi; Chen, Juan; Stefflova, Klara; Warren, Michael S.; Navab, Roya; Bandarchi, Bizhan; Mullins, Stefanie; Tsao, Ming; Cheng, Jonathan D.; Zheng, Gang.

In: Journal of Medicinal Chemistry, Vol. 52, No. 2, 22.01.2009, p. 358-368.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal