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.
Keywords: active targeting; biomimetic nanoparticle; hepatic stellate cell; hepatic stellate cell membrane; liver fibrosis.