title: Photodynamic therapy agent with a built-in apoptosis sensor for evaluating its own therapeutic outcome in situ.
abstract: Identifying the extent of apoptosis in cells or tissues after cancer therapy in real time would be a powerful firsthand tool for assessing therapeutic outcome. We combined therapeutic and imaging functions in one agent, choosing photodynamic therapy (PDT) as an appropriate cancer treatment modality. This agent induces photodamage in irradiated cells and simultaneously identifies apoptotic cells by near-infrared fluorescence. This photodynamic therapy agent with a built-in apoptosis sensor (PDT-BIAS) contains a fluorescent photosensitizer used as an anticancer drug, connected to a fluorescence quencher by a caspase-3 cleavable peptide linker. We demonstrated that cleavage of the peptide linker by caspase-3, one of the executioner caspases involved in apoptosis, results in a detectable increase of fluorescence in solution and in cancer cells after PDT treatment. The apoptosis involvement and drug effectiveness were confirmed by Apoptag and cell viability (MTT) assays supporting the ability of PDT-BIAS to induce and image apoptosis in situ.
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Klara
authors.initials: K
authors.lastname: Stefflova
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Diane
authors.initials: D
authors.lastname: Marotta
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012996:Solutions
chemical_list: D009842:Oligopeptides; D017319:Photosensitizing Agents; D012996:Solutions; C512437:pyropheophorbide a-glycyl-aspartyl-glutamyl-valyl-aspartyl-glycyl-seryl-glycyl-lysyl-(epsilon-BHQ-3); D002734:Chlorophyll; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases