Multifunctional RuO2 Sensitized Co3O4 Core‐Shell Sonozyme Heterojunctions for Sonodynamic and Nanocatalytic Co‐Amplified Immunotherapy

It is believed that reactive oxygen species (ROS)‐mediated immunogenic cell death (ICD) can promote DC maturation and initiate cytotoxic T lymphocytes infiltration, but the limited ROS generation and immunosuppressive tumor microenvironments (TME) restrict the effectiveness of sonodynamic and nanocatalytic therapy (SDT/NCT). Herein, RuO2 shell is utilized as the auxiliary sonosensitizers and nanozymes to sensitize Co3O4 core for the construction of core‐shell Co3O4@RuO2 heterojunction sonozymes. Enhanced sonodynamic and multienzyme‐mimic activities are observed in the heterojunction sonozymes, thanks to improved electron‐hole separation kinetics. Co3O4@RuO2‐triggered cascade amplification of antitumor immune response is realized by the heterojunction construction, GSH depletion, and relief of hypoxia co‐augmented ROS yield, which significantly induced a robust ICD effect. Significant antitumor effects have been observed to eliminate primary tumors and stop the growth of distant tumors through Co3O4@RuO2‐mediated SDT and NCT co‐amplified immunotherapy. This study provides promising insights into the development of heterojunction sonozymes as a novel antitumor nanoplatform to induce durable and potent immune responses.