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

IF 6.5 2区医学 Q1 NANOSCIENCE & NANOTECHNOLOGY

International Journal of Nanomedicine Pub Date : 2025-09-23 eCollection Date: 2025-01-01 DOI:10.2147/IJN.S533216

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

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引用次数: 0

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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mof介导的芦荟-大黄素递送通过焦亡和免疫抑制剂协同作用增强肝癌免疫治疗。

目的：肝细胞癌（HCC）仍然是全球主要的肿瘤负担，传统治疗方法疗效有限。本研究旨在利用焦亡缓解肿瘤免疫抑制微环境，增强全身免疫，提高免疫治疗效果，重点研究焦亡诱导剂、免疫治疗剂和给药策略的精准选择。方法：合成AE-FeMn/FA后，对其形貌、粒径和Zeta电位进行表征。我们评估了其活化H2O2产生·OH的催化性能，引发细胞焦亡的能力，以及体外/体内抗肿瘤作用。结合BMS-202，我们探索了PD-1/PD-L1复合物的抑制和协同诱导焦亡的作用。结果：静脉注射AE- femn /FA靶向肝癌，AE释放可控，可触发细胞焦亡和抗肿瘤免疫。BMS-202可缓解免疫抑制，增强AE-FeMn/ fa诱导的抗肿瘤反应，实现免疫介导的协同消除癌细胞。结论：焦亡联合增强免疫治疗纳米平台的协同方法有望成为一种有效的HCC免疫治疗策略，具有显著的临床转化潜力。未来的研究将优化平台，开展临床试验。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY

CiteScore

14.40

自引率

3.80%

发文量

511

审稿时长

1.4 months

期刊介绍： The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.