Targeting Liver Fibrosis with Nanoparticle Technology: The Dual-Drug Strategy for Hepatic Stellate Cell Activation Inhibition

Hepatic stellate cells (HSCs) are pivotal in the pathogenesis and progression of liver fibrosis. Their activation is characterized by increased expression of integrin receptor α_vβ3 and elevated intracellular oxidative stress, leading to extracellular matrix deposition. To address these challenges, we developed a nanotechnology-driven drug delivery system for the targeted transport of curcumin (CUR) and dihydromyricetin (DHM), two potential antifibrotic drugs with anti-inflammatory and antioxidant properties, into activated HSCs. Our results demonstrated that intravenously administered cyclo-RGD peptide (cRGDfk)-modified drug-loaded nanoparticles (NPs) effectively targeted fibrotic liver tissues, particularly activated HSCs. These drug-loaded NPs inhibited HSC activation and migration, induced apoptosis in activated HSCs, and downregulated α-SMA expression. In a carbon tetrachloride (CCl₄)-induced liver fibrosis model, the NPs exhibited significant antifibrotic effects and reduced the number of Ly6C^hi monocyte-derived macrophages in the liver. These findings suggest that cRGDfk-modified NPs carrying CUR and DHM have potential clinical applications in liver fibrosis therapy.