Unimolecular Photodynamic Nanoassembly for Amplified Photoimmunotherapy via Expanded ROS Generation and Hypoxia Reversal

Photodynamic therapy (PDT), a promising noninvasive antitumor therapeutic approach, can directly kill cancer cells and trigger an immunogenic cell death (ICD) effect by generating reactive oxygen species (ROS) and the cascade reactions of antitumor immunity. However, the hypoxic tumor microenvironment severely compromises the efficacy of PDT. To address this challenge, a self-oxycarrying nanoassembly POFF integrating the Type-I NIR photosensitizer tetrafluorophenyl bacteriochlorin (FBC) and an oxygen-carrying perfluorocarbon moiety was developed for amplified photoimmunotherapy via expanded ROS generation and hypoxia reversal. The nanoassembly exhibited "self-oxycarrying" capability and both enhanced Type-I and Type-II photodynamic performance to effectively alleviate hypoxia. Furthermore, in vitro and in vivo studies demonstrated that POFF possessed potent antitumor activity upon 750 nm laser light irradiation. The PDT-induced destruction of cancer cells released tumor-associated antigens, which, in turn, triggered a robust antitumor immune response and promoted the eradication of residual malignant cells. Collectively, this nanoassembly not only ameliorates the hypoxic tumor microenvironment but also provides a promising strategy to amplify the efficacy of photodynamic immunotherapy.