CaCO₃-MnSiO_x hybrid particles to enable CO₂-mediated combinational tumor therapy

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 MnSiO_x, for synergistic tumor inhibition combining enhanced catalytic effect and calcium overload. In this system, MnSiO_x 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.