[Rational design and translational applications of hepatitis B virus-like particles]

Hepatitis B virus-like particles (HBV-VLPs), characterized by precise biomimetic topological architecture and favorable biocompatibility, have become a highly promising cutting-edge carrier in nanomedicine and immune engineering. This article systematically summarizes the latest research progress in HBV-VLPs, with focuses on the structural biological characteristics and assembly mechanisms of hepatitis B surface antigens (HBsAg) and hepatitis B core antigens (HBcAg) of HBV and the engineering strategies for expression platforms and surface functionalization modifications. In view of the challenges of assembly heterogeneity and immune response differences in the clinical applications of HBV-VLPs, this article predicts the application prospects of VLPs in reversing immune tolerance of chronic hepatitis B and constructing a liver-targeted intelligent delivery platform. Considering our empirical research on the construction of bivalent chimeric VLPs and their activation of humoral and cellular immunity, this article discusses the translational potential of transferring the multivalent co-display strategy to the HBV-VLPs system for solving immune escape. Finally, we propose a design concept for VLPs from artificial intelligence (AI)-assisted computational structural biology, aiming to provide a theoretical basis and design ideas for the development of the next generation of efficient, controllable, and multifunctional nanobiologics.