Bifunctional Nano‐Assembly of Iridium(III) Phthalocyanine Complex Encapsulated with BSA: Hypoxia‐relieving/Sonosensitizing Effects and their Immunogenic Sonodynamic Therapy

Abstract Alleviating the hypoxia of tumor cells would be an effective strategy to improve the efficiency of sonodynamic therapy (SDT). Here, an Ir(III) phthalocyanine complex (IrPc) is synthesized and characterized, with which a nano‐assembly (IrPc‐NPs) is prepared by encapsulating its aggregates with BSA. IrPc‐NPs exhibit bifunctionality, catalysis on H₂O₂ decomposition to evolve O_2, and sonosensitization to generate ¹O₂ both in vitro and in vivo. The bifunctionality concertedly and synergistically boosts the efficacy of SDT by alleviating the hypoxia of tumor cells. Its amplifying effect on photoacoustic signal provides a tool to monitor the accumulation of the nano‐assembly in a tumor that guides timely the application of ultrasonic (US) irradiation during SDT treatment. These results also suggest that immunogenic cell death‐mediated immunotherapy for tumor cells is attributed to the efficacy of SDT induced by IrPc‐NPs. IrPc‐NPs exhibit excellent biocompatibility in vitro, benignancy in vivo toward the overall growth of the tumor‐bearing mice inoculated with 4T1 cells and the controllability on timely applying US irradiation during their treatment with IrPc‐NPs renders the nanosystem great potentials in developing into a clinic drug for immunogenic sonodynamic therapy.