通过金属有机框架增强 TLR7/8 激动剂的递送以治疗乙型肝炎病

StephenW

通过金属有机框架增强 TLR7/8 激动剂的递送以治疗乙型肝炎病毒
王丽媛 1 2 , 张桂强 3 4 , 孙杨 1 , 吴专昌 1 , 任财月 1 , 张兆英 1 , 彭雪琪 1 , 张彦坤 1 , 赵英 1 , 李春阳 1 5 , 高立芬 1 5 , 梁晓红1 5 , 孙海峰 3 , 崔继伟 3 , 马春红 1 5
隶属关系
隶属关系

    1
    山东大学齐鲁医学院基础医学院基础医学学院免疫学教育部重点实验室, 山东济南 250012
    2
    潍坊医科大学微生物学系,山东潍坊261042
    3
    山东大学化学化工学院, 胶体与界面化学教育部重点实验室, 济南 250100
    4
    山东第一医科大学山东省医学科学院科技创新中心,山东济南 250117
    5
    山东大学山东省感染与免疫重点实验室,山东济南250012

    PMID：36206454 DOI：10.1021/acsami.2c11203

抽象的

由于治疗效果不理想、现有疗法的副作用和免疫耐受性，乙型肝炎病毒 (HBV) 感染仍然是全球健康面临的主要挑战。 Toll 样受体 7/8 (TLR7/8) 激动剂在慢性乙型肝炎 (CHB) 治愈中显示出巨大潜力，但由于快速分散到微血管系统中，全身给药通常会引起严重的副作用。在此，我们将基于咪唑喹啉的 TLR7/8 激动剂 (IMDQ) 封装到沸石咪唑酯骨架 8 纳米颗粒 (IMDQ@ZIF-8 NPs) 中，用于 HBV 免疫治疗。与游离 IMDQ 相比，IMDQ@ZIF-8 NPs 在肝脏中有效积聚并被抗原呈递细胞 (APCs) 选择性吸收，从而在 HBV 感染模型中增强 APC 活化和有效清除病毒。引人注目的是，MDQ@ZIF-8 NP 治疗导致 HBV 感染小鼠明显产生抗 HBs 抗体和血清转换。总体而言，这项关于简便组装方法和有效治疗效果融合的研究代表了一种有前途的 HBV 治疗策略。

关键词：TLR7/8激动剂； ZIF-8 纳米粒子；乙型肝炎病毒;免疫疗法；肝脏堆积。

StephenW

Enhanced Delivery of TLR7/8 Agonists by Metal-Organic Frameworks for Hepatitis B Virus Cure
Liyuan Wang  1   2 , Guiqiang Zhang  3   4 , Yang Sun  1 , Zhuanchang Wu  1 , Caiyue Ren  1 , Zhaoying Zhang  1 , Xueqi Peng  1 , Yankun Zhang  1 , Ying Zhao  1 , Chunyang Li  1   5 , Lifen Gao  1   5 , Xiaohong Liang  1   5 , Haifeng Sun  3 , Jiwei Cui  3 , Chunhong Ma  1   5
Affiliations
Affiliations

    1
    Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China.
    2
    Department of Microbiology, Weifang Medical University, Weifang, Shandong 261042, China.
    3
    Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China.
    4
    Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong 250117, China.
    5
    Key Laboratory of Infection and Immunity of Shandong Province, Shandong University, Jinan, Shandong 250012, China.

    PMID: 36206454 DOI: 10.1021/acsami.2c11203

Abstract

Hepatitis B virus (HBV) infection remains a major challenge to global health due to unsatisfactory treatment efficacy, side effects of current therapies, and immune tolerance. Toll-like receptors 7/8 (TLR7/8) agonists have shown great potential in chronic hepatitis B (CHB) cure, but systemic administration often induces severe side effects due to rapid dispersion into the microvasculature. Herein, we encapsulate an imidazoquinoline-based TLR7/8 agonist (IMDQ) into zeolitic imidazolate framework 8 nanoparticles (IMDQ@ZIF-8 NPs) for HBV immunotherapy. Compared with free IMDQ, IMDQ@ZIF-8 NPs efficiently accumulate in the liver and are selectively taken up by antigen-presenting cells (APCs), leading to enhanced APC activation and efficient viral elimination in HBV-infected models. Strikingly, MDQ@ZIF-8 NP treatment results in the obvious production of anti-HBs antibody and seroconversion in HBV-infected mice. Overall, this study on the convergence of a facile assembly approach and efficient therapeutic effects represents a promising strategy for HBV treatment.

Keywords: TLR7/8 agonist; ZIF-8 nanoparticles; hepatitis B virus; immunotherapy; liver accumulation.