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

Photosensitizers (PSs) capable of <i>in situ</i> 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 <i>in situ</i> 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 π-π 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 <i>in situ</i>, 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.