title: Development of enzyme-activated photosensitizer based on intramolecular electron transfer.
abstract: Photosensitizers produce cytotoxic reactive oxygen species (ROS) upon light illumination, but it is difficult to ablate cells of a specific type (e.g., tumor cells) in the presence of other cell populations, because of the limited precision with which light illumination can be directed to small areas. Here, we report a strategy to achieve cell type-specific ablation by using an enzyme-activated off/on switch for oxidative stress induction. In the unactivated photosensitizer, induction of oxidative stress is quenched by intramolecular electron transfer. However, the target cells express an enzyme that hydrolyzes a substrate moiety of the photosensitizer and the activated photosensitizer induces oxidative stress. As proof of concept, we designed and synthesized a xanthene-based photosensitizer, TGI-betaGal, whose oxidative stress induction ability is switched on following hydrolysis reaction with beta-galactosidase, a widely used gene marker. TGI-betaGal could selectively ablate lacZ-positive cells, whereas it showed no toxicity to lacZ-negative cells, upon light illumination.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Yogo
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Urano
authors.forename: Mako
authors.initials: M
authors.lastname: Kamiya
authors.forename: Kiminari
authors.initials: K
authors.lastname: Sano
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagano
mesh_terms: D002460:Cell Line; D004579:Electron Transport; D004789:Enzyme Activation; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008027:Light; D018384:Oxidative Stress; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000633:toxicity; D014966:Xanthenes / Q000737:chemistry / Q000633:toxicity; D001616:beta-Galactosidase / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D014966:Xanthenes; D001616:beta-Galactosidase