Boosting Theranostic Performance of AIEgens Using Nanocatalyzer for Robust Cancer Immunotherapy

Abstract High‐performance theranostic systems are of paramount importance for achieving precise image‐guided cancer immunotherapy. Here, a novel nanoplatform is presented that integrates aggregation‐induced emission luminogen (AIEgen) with prussian blue (PB) nanocatalyzer for robust cancer immunotherapy. The AIEgen with dimethylamine substitution demonstrates compelling near‐infrared (NIR) light‐induced photothermal conversion and photodynamic therapy (PDT) capabilities. By incorporating AIEgen into porous PBNPs, and further enveloped within M1 macrophage membrane, a tumor‐specific theranostic nanoagent is constructed. This strategic integration effectively constrains the molecular motion of AIEgen, leading to amplified NIR‐II fluorescence brightness and PDT attributes. Moreover, PBNPs can catalyze tumor‐overexpressed H₂O₂ to generate oxygen to boost PDT efficacy, and PB's NIR absorption also intensifies photoacoustic imaging and photothermal effect. The integration of NIR‐II fluorescence and photoacoustic imaging provides comprehensive information for photoimmunotherapy in orthotopic breast cancer‐bearing mice. Leveraging its potent immunogenic cell death effect, the nanoagent not only significantly inhibits cancer growth, but also generates a whole‐cell therapeutic cancer vaccine to protect mice from tumor rechallenge. In highly malignant post‐surgery breast cancer models, the nanoagent enables both accurate identification of residual tumors and efficient inhibition of postoperative tumor recurrence and pulmonary metastasis. This study will offer valuable insights for creating highly efficacious and multifaceted photoimmunotherapy protocols.