Photoelectron Transfer at ZnTPyP Self-Assembly/TiO₂ Interfaces for Enhanced Two-Photon Photodynamic Therapy

Two-photon (TP) absorption nanomaterials are highly desirable for deep-tissue clinical diagnostics and orthotopic disease treatment. Here, a well-designed core/shell nanostructure was successfully synthesized with a ZnTPyP self-assembly nanocrystal (ZSN) inner core coated by a homogeneous TiO₂ layer outside (ZSN-TO). The ZSN is a good photosemiconductor, showing both one-photon (OP) and TP absorption properties for red fluorescence emission and electron-hole pair generation; TiO₂ with good biocompatibility acts as the electron acceptor, which can transfer photoelectron from ZSN to TiO₂ for highly effective electron-hole separation, favoring the production of long-life superoxide anion (O₂^•-) by electrons and oxygen and strong oxidizing hydroxyl radical (•OH) by holes and surrounding H₂O. Once pretreated with ZSN-TO, the simultaneous OP-405 nm or TP-800 nm laser stimulation and fluorescent imaging of reactive oxygen species (ROS) showed dynamical and continuous generation of ROS in HeLa cells, with cytotoxicity significantly increasing via the type-1-like photodynamic therapy process. The results demonstrated that the combination of organic ZSN with inorganic TiO₂ has great applications as an excellent photosensitizer for deep-tissue fluorescent imaging and noninvasive disease treatment via TP photodynamic therapy.