中国科学院长春应用化学研究所林君团队发现，琥珀酸盐纳米材料通过激活细胞焦亡和增强MHC-I表达来促进肿瘤免疫治疗。相关研究成果于2025年1月2日发表于国际顶尖学术期刊《美国化学会杂志》。

尽管免疫疗法的临床应用前景广阔，但其有效性往往受到低免疫反应和肿瘤免疫逃逸的限制。

该文中，研究人员介绍了一种简单、无毒的无机纳米材料琥珀酸钠（C₄H₄Na₂O₄ NPs），该材料采用快速微乳液方法制备，以增强癌症免疫治疗。合成的C₄H₄Na₂O₄ NPs可以向肿瘤细胞释放高浓度的Na⁺和琥珀酸离子，导致细胞内渗透压增加。

这会触发焦亡途径，导致细胞内容物、炎症因子和损伤相关分子模式的释放，最终增强免疫反应。此外，C₄H₄Na₂O₄ NPs通过上调主要组织相容性复合物-I（MHC-I）的表达来抑制肿瘤免疫逃逸。总的来说，C₄H₄Na₂O₄ NPs通过焦亡诱导的免疫激活和MHC-I表达上调缓解肿瘤免疫逃逸，显著抑制肿瘤生长和转移。

该项研究提供了一种利用MHC-I表达和焦下垂进行肿瘤治疗的新方法，证明了其在癌症免疫疗法中的临床应用潜力。

附：英文原文

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

Author: Pan Zheng, Guanglei Wang, Bin Liu, He Ding, Binbin Ding, Jun Lin

Issue&Volume: January 2, 2025

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.

DOI: 10.1021/jacs.4c09566

Source: https://pubs.acs.org/doi/full/10.1021/jacs.4c09566