Succinate Nanomaterials Boost Tumor Immunotherapy via Activating Cell Pyroptosis and Enhancing MHC-I Expression.

Despite the promising clinical applications of immunotherapy, its effectiveness is often limited by low immune responses and tumor immune escape. In this study, we introduce a simple and drug-free inorganic nanomaterial, sodium succinate (CHNaO NPs), prepared using a rapid microemulsion method to enhance cancer immunotherapy. The synthesized CHNaO NPs can release high concentrations of Na and succinate ions into tumor cells, leading to an increase in intracellular osmolarity. This triggers the pyroptosis pathway, resulting in the release of cellular contents, inflammatory factors, and damage-associated molecular patterns, which ultimately boost immune responses. Furthermore, CHNaO NPs inhibit tumor immune escape through upregulating major histocompatibility complex-I (MHC-I) expression. Collectively, CHNaO NPs significantly inhibit tumor growth and metastasis by pyroptosis-induced immune activation and MHC-I expression upregulation-remitted tumor immune escape. This research offers a novel approach to tumor treatment that leverages MHC-I expression and pyroptosis, demonstrating the potential for clinical application in cancer immunotherapy.