Multifunctional RuO ₂ Sensitized Co ₃ O ₄ Core‐Shell Sonozyme Heterojunctions for Sonodynamic and Nanocatalytic Co‐Amplified Immunotherapy

Abstract 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, RuO ₂ shell is utilized as the auxiliary sonosensitizers and nanozymes to sensitize Co ₃ O ₄ core for the construction of core‐shell Co ₃ O ₄ @RuO ₂ heterojunction sonozymes. Enhanced sonodynamic and multienzyme‐mimic activities are observed in the heterojunction sonozymes, thanks to improved electron‐hole separation kinetics. Co ₃ O ₄ @RuO ₂ ‐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 Co ₃ O ₄ @RuO ₂ ‐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.