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

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Title: MOF-Mediated Aloe-Emodin Delivery Enhances Hepatocellular Carcinoma Immunotherapy via Pyroptosis and Immunosuppressant Synergy
Authors: Xie H, Yi X, Huang K, Luo J, Zeng Q, He F, Wang L
Source: International Journal of Nanomedicine, Vol 20, Iss Issue 1, Pp 11647-11667 (2025)
Publisher Information: Dove Medical Press, 2025.
Publication Year: 2025
Collection: LCC:Medicine (General)
Subject Terms: Aloe-Emodin, Microenvironment response, Pyroptosis, Immunosuppressor, BMS-202, Medicine (General), R5-920
Description: Huaying Xie,* Xiaoyuan Yi,* Kunzhao Huang, Jianzhang Luo, Qingyu Zeng, Feifei He, Liyan Wang Digestive Department, Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyan Wang, Affiliated Hospital of Guilin Medical University, Lequn Road No. 15, Xiufeng District, Guilin, 541001, People’s Republic of China, Tel +86 15295953938, Email 168wangliyan@163.comPurpose: 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.Keywords: aloe-emodin, microenvironment response, pyroptosis, immunosuppressor, BMS-202
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1178-2013
Relation: https://www.dovepress.com/mof-mediated-aloe-emodin-delivery-enhances-hepatocellular-carcinoma-im-peer-reviewed-fulltext-article-IJN; https://doaj.org/toc/1178-2013
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  Data: Huaying Xie,* Xiaoyuan Yi,* Kunzhao Huang, Jianzhang Luo, Qingyu Zeng, Feifei He, Liyan Wang Digestive Department, Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyan Wang, Affiliated Hospital of Guilin Medical University, Lequn Road No. 15, Xiufeng District, Guilin, 541001, People’s Republic of China, Tel +86 15295953938, Email 168wangliyan@163.comPurpose: 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.Keywords: aloe-emodin, microenvironment response, pyroptosis, immunosuppressor, BMS-202
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