Rhein-based Pickering emulsion for hepatocellular carcinoma:Shaping the metabolic signaling and immunoactivation in transarterial chemoembolization  

作　　者：Xiaoliu Liang Hui Liu Hu Chen Xuqi Peng Zhenjie Li Minglei Teng Yisheng Peng Jiwei Li Linyu Ding Jingsong Mao Chengchao Chu Hongwei Cheng Gang Liu 

机构地区：[1]State Key Laboratory of Infectious Disease Vaccine Development,Xiang An Biomedicine Laboratory,National Innovation Platform for Industry-Education Integration in Vaccine Research,State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics,Center for Molecular Imaging and Translational Medicine,School of Public Health,Xiamen University,Xiamen,China [2]Department of Respiratory,Critical Care and Sleep Medicine,Xiang’an Hospital of Xiamen University,School of Medicine,Xiamen University,Xiamen,China [3]Eye Institute of Xiamen University,Fujian Provincial Key Laboratory of Ophthalmology and Visual Science,Xiamen University,Xiamen,China [4]Zhuhai UM Science&Technology Research Institute,Institute of Applied Physics and Materials Engineering,University of Macao,Macao SAR,China

出　　处：《Aggregate》2024年第4期319-338,共20页聚集体（英文）

基　　金：Major State Basic Research Development Program of China,Grant/Award Number:2023YFB3810000;National Natural Science Foundation of China,Grant/Award Numbers:U22A20333,81925019,U1705281,82202330;Fundamental Research Funds for the Central Universities,Grant/Award Numbers:20720190088,20720200019;Science Foundation of Fujian Province,Grant/Award Number:2020Y4003;Program for New Century Excellent Talents in University,China,Grant/Award Number:NCET-13-0502。

摘　　要：The efficacy of transarterial chemoembolization(TACE)has been limited by insufficient embolization and a high incidence of tumor recurrence.Herein,we iden-tified that aberrant metabolic reprogramming and immunosuppression contribute to TACE refractoriness and Rhein,as a potential glycolytic metabolism inhibitor and immunoactivation inducer,was optimized to sensitize tumors to TACE therapy.To achieve efficient embolization,we developed an oil-in-water lipiodol embolic emulsion by stabilizing the self-assembled Rhein nanogel.The assembled Rhein exhibited a nanofiber network,and its integration enhanced the mechanical stability and viscoelasticity of the lipiodol embolic agent.With the synergistic advantages of solid and liquid embolic agents,this carrier-free Pickering emulsion exhibits effi-cient embolization and sustained drug release in models of unilateral renal artery embolization,rabbit ear tumor embolization,rabbit orthotopic liver cancer,and rat orthotopic liver cancer.Compared to conventional three-way catheter mixing meth-ods,multimodal imaging corroborates a marked enhancement in local drug retention and tumor suppression.Importantly,the incorporation of Rhein-mediated syner-gistic immunoembolization in this strategy achieved efficient embolization while robustly activating anti-tumor immune responses,including inducing immunogenic cell death,dendritic cell activation,and major histocompatibility complex class I pre-sentation to CD8^(+)T cells for tumor killing.Together,thesefindings reveal a novel strategy for the application of self-assembled Rhein nanofiber-stabilized lipiodol emulsion to control metabolic signaling and immunoactivation in TACE.

关 键 词：GLYCOLYSIS hepatocellular carcinoma immunoembolization Pickering emulsion transarterial chemoem-bolization 

分 类 号：R735.7[医药卫生—肿瘤]