Multifunctional RuO ₂ Sensitized Co ₃ O ₄ 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.