Immunomodulating Sonocatalytic Nanoagents with Dual‐Functional Ir‐N Centers and Narrow Bandgap for Reversing Immunosuppression and Potentiating Ovarian Cancer Immunotherapy

Abstract The heterogeneity and immunosuppression microenvironment of ovarian cancer seriously restrict the efficiency of monomodal treatment. Emerging multimodal therapy strategies based on sonodynamic therapy with enhanced antitumor effects have attracted intensive attention in the quest to combat cancer. However, exploring highly efficient sonosensitizers integrating chemodynamic/sonodynamic/immunotherapies with reversing immunosuppressive tumor microenvironment (TME) capacity is urgently desired but remains challenging. Here, a facile strategy is designed to synthesize immunomodulating sonocatalytic nanoagents (IrT‐SCN) with dual‐functional Ir‐N centers and narrow bandgap for reversing immunosuppression and potentiating ovarian cancer immunotherapy. IrT‐SCN with dual‐functional centers Ir‐N₂ and Ir‐N₄ and conjugated networks show a reduced bandgap, moderate interaction with H₂O₂, and efficient production of reactive oxygen species (ROS). Such ROS capabilities include: 1) utilizing H₂O₂ in TME to catalytically generate potent O₂, as well as abundant superoxide anion (•O₂⁻) and singlet oxygen (¹O₂) radicals; 2) external ultrasound (US) irradiation can also boost the production of ¹O₂ simultaneously; 3) M1 polarization of tumor‐associated macrophages and enhanced immune effect can promote the outcome of cancer treatment. This finding provides proof‐of‐concept evidence for the future development of immunomodulating sonocatalytic nanoagents for oncological treatments and other ROS‐related biomedical fields.