Protease-triggered photosensitizing beacon based on singlet oxygen quenching and activation.
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.
Chen
Juan
J
Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Stefflova
Klara
K
Niedre
Mark J
MJ
Wilson
Brian C
BC
Chance
Britton
B
Glickson
Jerry D
JD
Zheng
Gang
G
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
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