Development of enzyme-activated photosensitizer based on intramolecular electron transfer

作者：Yogo Takatoshi; Urano Yasuteru; Kamiya Mako; Sano Kiminari; Nagano Tetsuo^*

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(15): 4320-4323.

DOI：10.1016/j.bmcl.2010.06.091

• Photosensitizer
• beta-Galactosidase
• Electron transfer
• Oxidative stress

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-beta Gal, whose oxidative stress induction ability is switched on following hydrolysis reaction with beta-galactosidase, a widely used gene marker. TGI-beta Gal could selectively ablate lacZ-positive cells, whereas it showed no toxicity to lacZ-negative cells, upon light illumination.

• 出版日期2010-8-1