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

Abstract

Photosensitizers (PSs) capable of in situ oxygen (O 2 ) 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 O 2 and singlet oxygen ( 1 O 2 ) 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 ( 3 PS*). These holes effectively oxidize water into O 2 in situ, which then participates in downstream photosensitization with 3 PS* to yield 1 O 2 . This cascade reaction affords PTA NPs with continuous O 2 supply and efficient 1 O 2 production, enabling a 63.07% higher antibacterial rate compared with the clinical antibiotic vancomycin.