<p>The high content of glutathione (GSH) and the deficiency of hydrogen peroxide (H₂O₂) in tumor cells seriously affect the efficiency of chemodynamic therapy (CDT). Developing a tumor-specific CDT therapeutic agent that can continuously supply H₂O₂ and deplete GSH is of great significance for increasing the production rate of reactive oxygen species (ROS) and improving the efficiency of CDT. Herein, we propose a self-supplying H₂O₂ and highly efficient catalytic integrated CDT therapeutic platform. By constructing a CuO₂-coated cobalt-doped ZIF-8 nanoplatform (CuO₂@Co/ZIF-8), achieve self-supplying H₂O₂ and GSH depletion for efficient breast cancer treatment. The tumor micro-acidic environment triggers the decomposition of CuO₂, continuously supplying H₂O₂ and generating Cu²⁺, while Cu²⁺ consumes GSH to form Cu⁺. Co²⁺ and Cu⁺ catalyze the generation of ∙OH from H₂O₂. This synergistic mechanism not only overcomes the limitations of single materials in H₂O₂ supply and catalytic efficiency, but also significantly enhances the therapeutic effect of CDT. Our work significantly improves the efficacy of CDT by optimizing the supply of H₂O₂ and catalytic efficiency. The synergistic application of Co/ZIF-8 and CuO₂ provides a new efficient and safe strategy for chemodynamic tumor therapy.</p> Graphical Abstract <p></p>