Photocatalytic Production of Hydrogen Peroxide in Hypoxic Cancer Cells Enabled by Loose Ordered-Assembled Photosensitizer

The stepwise reduction of oxygen into O 2 •–, H 2 O 2, and ·OH by photosensitizers (PSs) has a great advantage in killing cancer cells. Intensive attention has been drawn to how to initiate the first step of yielding O 2 •–, yet the following transformations have always been taken for granted. Herein, by regulating the assembly behavior of triphenylamine and pyridine salt-based PSs with different counteranions, the loose ordered-assembled structure of TPA-BPh 4 accomplished the production of H 2 O 2 and ·OH, while only O 2 •– but no ·OH can be detected for the other four PSs. The TPA-BPh 4 displayed an ordered arrangement with a larger intermolecular distance, favoring the adsorption of H 2 O on the TPA-BPh 4 and fostering the transformation into H 2 O 2 . The generated H 2 O 2 triggered the Haber–Weiss reaction to relieve intracellular hypoxia, efficiently killing cancer cells. This work provides a new avenue for the design of photosensitizers for the generation of H 2 O 2 and ·OH.