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 (C4H4Na2O4 NPs), prepared using a rapid microemulsion method to enhance cancer immunotherapy. The synthesized C4H4Na2O4 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, C4H4Na2O4 NPs inhibit tumor immune escape through upregulating major histocompatibility complex-I (MHC-I) expression. Collectively, C4H4Na2O4 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.