Calcium carbonate nanoplatform for remodeling the tumor microenvironment to enhance Chemo-Immunotherapeutic Synergy in breast cancer

• Enhancing tumor-specific immune responses and overcoming the immunosuppressive TME are key to improving the efficacy of cancer immunotherapy. • Ameliorating the immunosuppressive tumor microenvironment and regulating immune cell activity, promoting synergistic chemoimmunotherapeutic outcomes. • Calcium carbonate nanocarrier not only serves as a drug delivery vehicle but also neutralizes lactic acid in the tumor tissue. • Supplies supplemental arginine within the tumor tissue to increase the activation of effector T cells. Cancer immunotherapy currently represents the only promising strategy with the potential to achieve a complete cure for tumors. Enhancing tumor-specific immune responses and overcoming the immunosuppressive TME are key to improving the efficacy of cancer immunotherapy. In this study, we introduce a calcium carbonate-based nanocarrier capable of modulating the tumor microenvironment. This system is coloaded with L-arginine (L-Arg) and the chemotherapeutic agent doxorubicin (DOX), aiming to optimize the conventional chemoimmunotherapy approach by ameliorating the immunosuppressive tumor microenvironment and regulating immune cell activity, thereby promoting synergistic chemoimmunotherapeutic outcomes. Specifically, DOX directly kills tumor cells and induces immunogenic cell death. Moreover, the calcium carbonate nanocarrier not only serves as a drug delivery vehicle but also neutralizes lactic acid in the tumor tissue, thereby alleviating the acidic immunosuppressive microenvironment. Furthermore, it supplies supplemental arginine within the tumor tissue to increase the activation of effector T cells. Ultimately, this strategy achieves highly efficient antitumor efficacy through the combined and synergistic actions of chemotherapy and immunotherapy.