Development of a High-Stability Protein Co-Assembled Superoxide Anion Generator for Near-Infrared-II Imaging-Guided Photodynamic Therapy

Oxygen concentration and penetration depth are the two key factors that influence the therapeutic effect of photodynamic therapy (PDT) in hypoxic tumors. Developing a simple strategy to construct advanced type I photosensitizers (PSs) with near-infrared region (NIR) absorption has a wide application prospect but remains a challenge. Herein, based on simple D-π-A conjugated CQ-SO3 and CQ-S-SO3, bovine serum albumin (BSA) was elaborately selected to construct the supramolecular assemblies CQ-SO3@BSA and CQ-S-SO3@BSA. Encouragingly, the high-stability CQ-S-SO3@BSA exhibited superior superoxide anion (O2‑•) generation and activated three-photon fluorescence properties (1240 nm excitation). Confocal microscopy imaging indicated that CQ-S-SO3@BSA can specifically target cancer cell membranes and penetrate 120 µm tissue depth, triggering cancer cell apoptosis under NIR-II light irradiation even in a hypoxic environment. This discovery emphasizes the potential for “killing two birds with one stone” based on supramolecular assembly, thereby opening up new possibilities for phototherapy.