代谢重编程作为癌症的特征之一，与肿瘤的发生、生长或迁移有关，代谢途径的调节已成为癌症治疗的一种新方法。然而，肿瘤细胞中传统的代谢介导的细胞凋亡过程表现出有限的免疫原性和抗肿瘤免疫的激活不足。在此，成功制备了磷脂包被的柠檬酸钠纳米粒子（PSCT NPs），其溶解在肿瘤细胞中，然后释放大量的柠檬酸根离子和Na离子。大量离子导致细胞内渗透压升高，从而激活 caspase-1/gasdermin D (GSDMD) 介导的细胞焦亡途径。同时，柠檬酸盐诱导 caspase-8/gasdermin C (GSDMC) 通路的激活。这两种途径的联合作用协同引起强烈的细胞焦亡，表现出显着的抗肿瘤免疫反应和肿瘤生长抑制。这一发现为纳米材料在调节新陈代谢和改变细胞死亡模式以增强抗肿瘤免疫治疗方面的潜力提供了新的见解。

Metabolic reprogramming, as one of the characteristics of cancer, is associated with tumorigenesis, growth, or migration, and the modulation of metabolic pathways has emerged as a novel approach for cancer therapy. However, the conventional metabolism-mediated apoptosis process in tumor cells exhibits limited immunogenicity and inadequate activation of antitumor immunity. Herein, phospholipid-coated sodium citrate nanoparticles (PSCT NPs) are successfully prepared, which dissolve in tumor cells and then release significant amounts of citrate ions and Na+ ions. Massive quantities of ions lead to increased intracellular osmotic pressure, which activates the caspase-1/gasdermin D (GSDMD) mediated pyroptosis pathway. Simultaneously, citrate induces activation of the caspase-8/gasdermin C (GSDMC) pathway. The combined action of these two pathways synergistically causes intense pyroptosis, exhibiting remarkable antitumor immune responses and tumor growth inhibition. This discovery provides new insight into the potential of nanomaterials in modulating metabolism and altering cell death patterns to enhance antitumor immunotherapy.