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

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.