Construction of Diverse Calcium‐Based Nanomaterials through a Microemulsion Method for Pyroptosis‐Initiated Antitumor Immunotherapy

Calcium-based nanomaterials have gained significant attention in biomedical fields due to their critical roles in biological processes and excellent biocompatibility. In this study, a universal and simple microemulsion approach is presented using calcium dodecylbenzenesulfonate as both surfactant and calcium source, enabling the synthesis of diverse calcium-based nanomaterials (e.g., calcium succinate, calcium hypophosphite, calcium metatungstate, calcium gluconate, calcium formate, and calcium citrate). To address the challenges of inadequate immune response in tumor immunotherapy, calcium succinate nanoparticle (PCS NP) is investigated as an example. The PCS NP exhibit enhanced immunotherapeutic potential by activating the caspase-1/GSDMD-mediated pyroptosis pathway via calcium overload, which in turn enhanced the immune response. Additionally, the anionic succinate component upregulates major histocompatibility complex-I (MHC-I) expression, enhancing antigen presentation and alleviating the immunosuppressive tumor microenvironment (TME). This microemulsion strategy provides a novel platform for calcium nanomaterial fabrication, opening new avenues for TME-regulated immunotherapy enhancement, demonstrating a broad application prospect.