Achieving efficient photodynamic therapy under both normoxia and hypoxia using cyclometalated Ru(<scp>ii</scp>) photosensitizer through type I photochemical process

Abstract

Photodynamic therapy (PDT) through the generation of singlet oxygen utilizing photosensitizers (PSs) is significantly limited under hypoxic conditions in solid tumors. So it is meaningful to develop effective PSs which can maintain excellent therapeutic effects under hypoxia. Here we reported a coumarin-modified cyclometalated Ru(ii) photosensitizer (<b>Ru2</b>), which exhibits lower oxidation potential and stronger absorption in the visible region than the coumarin-free counterpart. The evaluation of the PDT effect was performed under both normoxia and hypoxia. The results showed that <b>Ru2</b> has a better therapeutic effect than the coumarin-free counterpart in <i>in vitro</i> experiments. Especially under hypoxia, <b>Ru2</b> still retained an excellent PDT effect, which can be attributed to the direct charge transfer between the excited PS and an adjacent substrate through a type I photochemical process, forming highly-oxidative hydroxyl radicals to damage tumor cells. The anti-tumor activity of <b>Ru2</b> was further proven to be effective in tumor-bearing mice, and tumor growth was inhibited remarkably under PDT treatment.