title: Protease-triggered photosensitizing beacon based on singlet oxygen quenching and activation.
abstract: We report a new concept for type-II photosensitization, based on incorporating the photosensitizer (PS) and a singlet-oxygen (1O2) quenching/scavenging molecule onto a disease-targeting linker, such that the PS becomes activatable by light only when targeting has occurred. In this first proof-of-concept report, a model photosensitizing beacon was synthesized containing a pyropheophorbide as the PS and a carotenoid as the 1O2 quencher. These were kept in close proximity by the self-folding of a caspase-3-specific peptide sequence. Upon caspase-3-induced cleavage, the 1O2 production increased markedly, as measured directly by 1O2 near-infrared luminescence and lifetime measurements.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Klara
authors.initials: K
authors.lastname: Stefflova
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niedre
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: Britton
authors.initials: B
authors.lastname: Chance
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Glickson
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D002338:Carotenoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D008163:Luminescent Measurements; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D026082:Singlet Oxygen / Q000737:chemistry* / Q000378:metabolism
chemical_list: D061945:Caspase Inhibitors; D009842:Oligopeptides; D017319:Photosensitizing Agents; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D002734:Chlorophyll; D026082:Singlet Oxygen; C040298:pyropheophorbide a; D002338:Carotenoids; D053148:Caspase 3; D020169:Caspases