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

Abstract

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.