Cascade Production of In Situ Oxygen and Singlet Oxygen from Self-Assembled Nanophotosensitizer for Anti-Hypoxic Photodynamic Therapy

Photosensitizers (PSs) capable of in situ oxygen (O2) production are attractive for overcoming hypoxia in photodynamic therapy (PDT). However, these PSs generally require multiple components and complex fabrication procedures, preventing their clinical translation. Herein, we develop a single-component nanophotosensitizer via simple self-assembly that enables cascade production of in situ O2 and singlet oxygen (1O2) for superior antibacterial PDT (aPDT). Perylene tetracarboxylic acid (PTA) molecules self-assemble into nanophotosensitizers (PTA NPs). Mechanism studies reveal dual functionality of PTA NPs due to their antiparallel-displaced pi-pi stacking. Aggregated PTA molecules undergo intermolecular electron transfer to yield substantial photogenerated holes, while unimolecular PTA undergoes intersystem crossing to produce triplet PS (3PS*). These holes effectively oxidize water into O2 in situ, which then participates in downstream photosensitization with 3PS* to yield 1O2. This cascade reaction affords PTA NPs with continuous O2 supply and efficient 1O2 production, enabling a 63.07% higher antibacterial rate compared with the clinical antibiotic vancomycin.