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Life sciences · Journal article
Small · September 23, 2026
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ABSTRACT While singlet oxygen ( 1 O 2 )‐based therapies like photodynamic therapy (PDT) demonstrate clinical anticancer efficacy, their dependence on external light and substantial O 2 consumption significantly limits their broader application. To surmount these constraints, we develop a chemiexcited (light‐independent) PDT platform by encapsulating bis[2,4,5‐trichloro‐6‐(pentyloxycarbonyl) phenyl] oxalate (CPPO) and chlorin e6 (Ce6) within the 1,2‐distearoyl‐ sn ‐glycero‐3‐phosphoethanolamine‐ N ‐[methoxy(polyethyleneglycol)‐2000] (ammonium salt) (DSPE‐PEG 2000 ‐OMe) micelle (termed CCM). The CCM is then incorporated along with vitamin C (Vc) into a Ca 2+ –alginate hydrogel, forming a final product denoted as CCMVH. Following intratumoral injection of CCMVH, the sustained Vc release continuously elevates the tumoral H 2 O 2 level. Subsequent reaction of H 2 O 2 with CPPO generates chemical energy, activating Ce6 to produce 1 O 2 without light. More importantly, we employ hyperbaric oxygen (HBO) to sustain the high intratumoral O 2 level during chemiexcited PDT. The synergy between Vc‐driven H 2 O 2 generation and HBO‐mediated O 2 supply creates a dual‐pronged amplification effect that significantly enhances 1 O 2 production. In addition, this light‐independent PDT induces marked immunogenic cell death, promotes the infiltration of antitumor immune cells, and reprograms the immunosuppressive tumor microenvironment, resulting in potent tumor inhibition. This work provides a facile strategy for overcoming the fundamental limitations of conventional PDT, offering a translatable approach for cancer immunotherapy.