title: Photodynamic molecular beacon triggered by fibroblast activation protein on cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers.
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.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Pui-Chi
authors.initials: PC
authors.lastname: Lo
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Klara
authors.initials: K
authors.lastname: Stefflova
authors.forename: Michael S
authors.initials: MS
authors.lastname: Warren
authors.forename: Roya
authors.initials: R
authors.lastname: Navab
authors.forename: Bizhan
authors.initials: B
authors.lastname: Bandarchi
authors.forename: Stefanie
authors.initials: S
authors.lastname: Mullins
authors.forename: Ming
authors.initials: M
authors.lastname: Tsao
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cheng
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases; D005347:Fibroblasts / Q000166:cytology; D005434:Flow Cytometry; D018093:Gelatinases; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins; D051379:Mice; D018613:Microscopy, Confocal; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D012697:Serine Endopeptidases / Q000502:physiology*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha