Hepatic Stellate Cell Membrane-Camouflaged Nanoparticles for Targeted Delivery of an Antifibrotic Agent to Hepatic Stellate Cells with Enhanced Antifibrosis Efficacy.

Abstract

Liver fibrosis is characterized by the excessive accumulation of extracellular matrix proteins primarily produced by activated hepatic stellate cells (HSCs). The activation of HSCs plays a pivotal role in driving the progression of liver fibrosis. Achieving specific targeted delivery of antifibrotic agents toward activated HSCs remains a formidable challenge. Here, we developed an HSC membrane-camouflaged nanosystem, named HSC-PLGA-BAY, for the precise delivery of the antifibrosis agent BAY 11-7082 to activated HSCs in the treatment of liver fibrosis. The designed HSC-PLGA-BAY nanosystem exhibited selective targeting toward activated HSCs, with internalization mediated by homologous cell adhesion molecules from the HSC membrane, namely integrins and N-cadherin. Furthermore, our findings demonstrate that treatment with HSC-PGA-BAY significantly increased apoptosis of activated HSCs and ameliorated liver fibrosis progression in a bile duct ligation (BDL)-induced fibrotic mice model. Collectively, the HSCs-targeted therapeutic platform holds promising potential as an effective strategy for liver fibrosis treatment.