Hollow RuO ₂ nanozymes sensitized by carbon dot sonosensitizers for sonodynamic/chemodynamic-activated immunotherapy

<b>Background:</b> Regulating the morphology structure of sonosensitizers and nanozymes is crucial to improve sonodynamic and enzyme-mimic activities. <b>Methods:</b> We report for the first time the utilization of Cu₂O nanospheres as the sacrificial templates for the synthesis of hollow RuO₂ nanospheres (H-RuO₂) for high-efficiency sonodynamic and chemodynamic therapy (SDT/CDT). We then utilized NIR phosphorescence carbon dots (CDs) as the auxiliary sonosensitizers to sensitize H-RuO₂ for the construction of CD@H-RuO₂ heterojunctions. <b>Results:</b> Compared with solid nanoparticles, nanosheets, and other structures, the hollow RuO₂ (H-RuO₂) nanostructures are expected to exhibit stronger catalytic activity due to their larger specific surface area and more catalytic active sites. The improved electron-hole separation kinetics enable CD@H-RuO₂ nanozymes with significantly enhanced sonodynamic and multienzyme-mimic activities. CD@H-RuO₂-triggered cascade amplification of antitumor immune response was realized by the heterojunction construction, GSH depletion, and relief of hypoxia co-augmented ROS yield, which significantly induced a robust ICD. <b>Conclusion:</b> CD@H-RuO₂-mediated SDT and CDT co-amplified immunotherapy have shown significant antitumor effects, resulting in the eradication of primary tumors and the inhibition of distant tumor growth. This study offers hopeful insights into the fabrication of heterojunctions for sonodynamic/chemodynamic-activated immunotherapy.