Mitochondria-targeted iridium-based photosensitizers enhancing photodynamic therapy effect by disturbing cellular redox balance.

Photodynamic therapy (PDT) is a non-invasive, light-activated treatment approach that has been broadly employed in cancer. Cyclometallic iridium (Ш) complexes are candidates for ideal photosensitizers due to their unique photophysical and photochemical features, such as high quantum yield, large Stokes shift, strong resistance to photobleaching, and high cellular permeability. We evaluated a panel of iridium complexes and identified PC9 as a powerful photosensitizer to kill cancer cells. PC9 shows an 8-fold increase of cytotoxicity to HeLa cells under light irradiation. Further investigation discloses that PC9 has a strong mitochondrial-targeting ability and can inhibit the antioxidant enzyme thioredoxin reductase, which contributes to improving PDT efficacy. Our data indicate that iridium complexes are efficient photosensitizers with distinct physicochemical properties and cellular actions, and deserve further development as promising agents for PDT. [Display omitted] • The reported PC9 is an efficient photosensitizer for photodynamic therapy (PDT). • PC9 generates ROS under illumination and predominantly localizes in mitochondria. • Direct disruption of the redox system by PC9 is a further plus to its PDT effect. • A new vision to develop photosensitizers for PDT applications is presented. [ABSTRACT FROM AUTHOR]