Development of an Azo-based Photosensitizer Activated under Mild Hypoxia for Photodynamic Therapy.

Photodynamic therapy (PDT) utilizes photoirradiation in the presence of photosensitizers to ablate cancer cells via generation of singlet oxygen (O-1(2)), but it is important to minimize concomitant injury to normal tissues. One approach for achieving this is to use activatable photosensitizers that can generate O-1(2) only under specific conditions. Here, we report a novel photosensitizer that is selectively activated under hypoxia, a common condition in solid tumors. We found that introducing an azo moiety into the conjugated system of a seleno-rosamine dye effectively hinders the intersystem crossing process that leads to O-1(2) generation. We show that the azo group is reductively cleaved in cells under hypoxia, enabling production of O-1(2) to occur. In PDT in vitro, cells under mild hypoxia, within the range typically found in solid tumors (up to about 5% O-2), were selectively ablated, leaving adjacent normoxic cells intact. This simple and practical azobased strategy should be widely applicable to design a range of activatable photosensitizers.