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

Area of Science:

• Nanomedicine
• Hepatology
• Biotechnology

Background:

• Hepatic stellate cells (HSCs) drive liver fibrosis through activation, increased integrin αvβ3 expression, and oxidative stress.
• Extracellular matrix deposition by activated HSCs exacerbates liver fibrosis progression.

Purpose of the Study:

• To develop a nanotechnology-based drug delivery system for targeted antifibrotic therapy.
• To investigate the efficacy of curcumin (CUR) and dihydromyricetin (DHM) loaded nanoparticles (NPs) in inhibiting HSC activation and liver fibrosis.

Main Methods:

• Development of cyclo-RGD peptide (cRGDfk)-modified NPs loaded with CUR and DHM.
• Intravenous administration of NPs in a carbon tetrachloride (CCl4)-induced liver fibrosis model.
• Assessment of NP targeting, HSC inhibition, apoptosis induction, α-SMA downregulation, and antifibrotic effects.

Main Results:

• cRGDfk-modified NPs effectively targeted fibrotic liver tissues and activated HSCs.
• NPs inhibited HSC activation, migration, and induced apoptosis, downregulating α-SMA expression.
• The NPs demonstrated significant antifibrotic effects and reduced Ly6Chi monocyte-derived macrophages in vivo.

Conclusions:

• Targeted delivery of CUR and DHM via cRGDfk-modified NPs shows promise for treating liver fibrosis.
• This nanomedicine approach effectively targets activated HSCs, mitigating key fibrotic processes.
• The findings support the potential clinical application of these NPs in liver fibrosis therapy.