A dual-type I/II photosensitizer targeting the plasma membrane for photodynamic therapy.

Photodynamic therapy is a highly efficient approach for inducing tumor cell death through the generation of reactive oxygen species mediated by photosensitizers. However, conventional photosensitizers are largely confined to the oxygen-dependent Type II pathway and lack the capability to target specific subcellular structures. To address these limitations, this study presented the rational design of a cell membrane-targeted photosensitizer DAD, featuring a donor-π-acceptor architecture. In DAD, electron-donating group triphenylamine was conjugated via a carbon‑carbon double bond to pyridine-derived electron-accepting unit. Further incorporation of hydrophobic alkyl chain conferred amphiphilicity to DAD, enabling effective membrane anchoring on cells. Thanks to its aggregation-induced emission characteristics, DAD exhibited excellent photophysical properties. Upon visible light irradiation, DAD was capable of not only generating singlet oxygen via the Type II pathway, but also producing superoxide anions and hydroxyl radicals through the Type I mechanism, thereby offering the potential to overcome the limitations of photodynamic therapy efficacy associated with tumor hypoxia. More importantly, DAD specifically targeted the cell membrane and induced structural disruption of the membrane upon light exposure, leading to efficient tumor cell death. Therefore, this work provided valuable insights into the rational design of dual Type I/II photosensitizers and contributes to the development of cell membrane-targeted aggregation-induced emission photosensitizers for future cancer therapeutics.