Enhanced Delivery of TLR7/8 Agonists by Metal–Organic Frameworks for Hepatitis B Virus Cure

作者：Liyuan Wang, Guiqiang Zhang, Yang Sun, Zhuanchang Wu, Caiyue Ren, Zhaoying Zhang, Xueqi Peng, Yankun Zhang, Ying Zhao, Chunyang Li, Lifen Gao, Xiaohong Liang, Haifeng Sun, Jiwei Cui, Chunhong Ma · 发表于：ACS Applied Materials & Interfaces · 年份：2022 · DOI：10.1021/acsami.2c11203 · 被引用次数：13 · 研究领域：Hepatitis B Virus Studies、RNA Interference and Gene Delivery、Immunotherapy and Immune Responses

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.