A dual-targeting near-infrared biomimetic drug delivery system for HBV treatment

Hepatitis B virus (HBV) infection is a serious global public health threat. It remains elusive to achieve a functional HBV cure with currently available antivirals. Herein, a photo-responsive delivery vehicle composed of Nd³⁺ -sensitized core-shell upconversion nanoparticle (UCNP), mesoporous silica nanoparticle (MSN), antisense oligonucleotides (ASOs), and capsid-binding inhibitor C39 was established, which was named UMAC according to the initials of its components. Subsequently, the as-synthesized delivery vehicle was encapsulated by β- D-galactopyranoside (Gal) modified red blood cell (RBC) membrane vesicles, which enabled precise targeting of the liver cells (UMAC-M-Gal). Both in vitro and in vivo experiments demonstrated that this biomimetic system could successfully achieve controlled drug release under light conditions at 808 nm, leading to effective suppression of HBV replication in this dual-targeted therapeutic approach. Together, these results substantiate the system has huge prospects for application to achieve functional HBV cure, and provides a promising novel strategy for drug delivery.