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.