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Nanocatalysts mediated reactive oxygen species (ROS) based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects. However, the treatment outcome is limited by the efficiency of local catalytic reaction. Herein, we report a novel type of core–shell hybrid nanoparticles (CaCO3@MS), consisting of CaCO3 and MnSiOx, for synergistic tumor inhibition combining enhanced catalytic effect and calcium overload. In this system, MnSiOx serves as catalysts with glutathione (GSH) responsive Mn2+ ions release functionality. CaCO3 nanoparticles play three important roles, including carbon dioxide (CO2) donor, pH modulator, and Ca2+ overload agent. It is found that the CaCO3 nanoparticles can induce CO2 production and pH increase in acidic tumor environment, both of which promote Mn2+ mediated ROS generation. And simultaneous release of Ca2+ ions from CaCO3 triggers calcium overload in tumor, which functions collaboratively with excessive ROS to induce cancer cell apoptosis. The results demonstrate that after treatment with CaCO3@MS, a remarkable tumor inhibition was achieved both in vitro and in vivo, while no clear toxic effect was observed. This study has therefore provided a feasible effective approach to improve catalytic therapeutic efficacy by an “exogenous CO2 delivery” strategy for combinational tumor therapy.
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