Cascade Production of <i>In Situ</i> Oxygen and Singlet Oxygen from Self-Assembled Nanophotosensitizer for Anti-Hypoxic Photodynamic Therapy
Ruida Bai, Linfang Yang, Mingxuan Jia, Ruizhe Chen, Haolin Zhang, Yonghui Pan, Ping He, Xiaofei Miao, Quli Fan, Wenbo Hu
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.