Dual-Functional Artificial Peroxidases with Ferriporphyrin Centers for Amplifying Tumor Immunotherapies via Immunogenic Cell Death

Constructing highly effective sonosensitizers that integrate tumor microenvironment (TME)-adaptive and ultrasound (US)-controllable production of reactive oxygen species (ROS) to amplify tumor immunotherapies is extremely desirable but remains challenging. Here, inspired by the coordination structure and biocatalytic effects of Fe-based peroxidase, a dual-functional artificial peroxidase is synthesized with ferriporphyrin networks (FePorNW-DAP) to serve a TME-adaptive and US-controllable ROS-generator for amplifying tumor immunotherapies in breast cancer via immunogenic cell death. Owing to the structural advantages of the ferriporphyrin-based large d-pi-conjugated networks with the monatomic FeN4 coordination center, moderate interaction with H2O2, and decreased bandgap, the FePorNW-DAP displays efficient dual-functional ROS production capabilities to combat tumor cells and amplify the tumor immunotherapies, 1) utilize locally produced H2O2 in the TME to catalytically generate potent center dot OH and other ROS species; simultaneously, 2) external US irradiation can further boost the generation of center dot OH and 1O2. This work provides not only critical evidence that the proposed dual-functional artificial peroxidases can induce a strong antitumor immune response and immune memory but also offers essential guidance for creating a high-performance and biocompatible strategy to regulate the immunosuppression TME and enhance the antitumor immune responses of breast cancer. A dual-functional artificial peroxidase with ferriporphyrin networks (FePorNW-DAP) is synthesized to serve as a tumor microenvironment (TME)-adaptive and ultrasound (US)-controllable reactive oxygen species-generator for amplifying tumor immunotherapies. The FePorNW-DAP can significantly enhance immunogenic cell death, activate the immune system, and reprogram immunosuppressed TME, which leads to notable inhibition of the growth of primary and distant tumors and blocked lung metastases.image