MOF-Mediated Aloe-Emodin Delivery Enhances Hepatocellular Carcinoma Immunotherapy via Pyroptosis and Immunosuppressant Synergy

MOF介导的芦荟-大黄素递送通过细胞焦亡和免疫抑制剂的协同作用增强肝细胞癌免疫疗法

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作者:Huaying Xie # ,Xiaoyuan Yi # ,Kunzhao Huang ,Jianzhang Luo ,Qingyu Zeng ,Feifei He ,Liyan Wang

Abstract

Purpose: Hepatocellular carcinoma (HCC) remains a major global oncological burden, with conventional therapies showing limited efficacy. This study aimed to utilize pyroptosis to alleviate the tumor's immunosuppressive microenvironment, enhance systemic immunity, and improve immunotherapy efficacy, focusing on precise selection of pyroptosis inducers, immunotherapeutic agents, and drug delivery strategies. Methods: After synthesizing AE-FeMn/FA, its morphology, particle size, and Zeta potential were characterized. We evaluated its catalytic performance in activating H2O2 to produce ·OH, ability to trigger cellular pyroptosis, and in vitro/in vivo anti-tumor effects. Combined with BMS-202, we explored suppression of the PD-1/PD-L1 complex and synergistic induction of pyroptosis. Results: Intravenous AE-FeMn/FA targeted HCC, with controlled AE release triggering pyroptosis and anti-tumor immunity. BMS-202 alleviated immunosuppression, enhancing AE-FeMn/FA-induced anti-tumor responses, achieving synergistic immune-mediated cancer cell elimination. Conclusion: The synergistic approach of pyroptosis combined with an enhanced immunotherapy nanoplatform shows promise as an effective HCC immunotherapy strategy, with significant clinical translation potential. Future studies will optimize the platform and conduct clinical trials.

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