Potent Covalent Organic Framework Nanophotosensitizers with Staggered Type I/II Motifs for Photodynamic Immunotherapy of Hypoxic Tumors

Photodynamic therapy (PDT) using oxygen-dependent type II photosensitizers is frequently limited by the hypoxic microenvironment of solid tumors. Type I photosensitizers show oxygen-independent reactive oxygen species (ROS) generation upon light irradiation but still face the challenges of aggregation-caused quenching (ACQ) and low efficiency to produce ROS. Herein, we first prepare an efficient type I photosensitizer from a perylene derivative via intramolecular donor-acceptor binding and sulfur substitution, which significantly enhance intersystem crossing between singlet and triplet states and electron transfer capability. After reaction with a type II photosensitizer, the covalent organic framework (COF) nanophotosensitizer is formed with alternated type I and II photosensitizer motifs in the same layer and staggered AB stacking between layers to avoid ACQ. The nanophotosensitizer exhibits high-efficiency generation of singlet oxygen (