Ultrasound-Assisted Targeted Therapy for Liver Fibrosis Using Rosiglitazone-Loaded Lipid Nanoparticles Functionalized...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Hepatology

Background:

• Hepatic fibrosis involves excessive extracellular matrix accumulation, driven by activated hepatic stellate cells (aHSCs).
• Current liver fibrosis therapies suffer from poor targeting and systemic toxicity.
• Developing targeted, noninvasive treatment strategies is crucial for managing liver fibrosis.

Purpose of the Study:

• To develop and evaluate a novel nanodrug delivery system for targeted ultrasound-assisted therapy of liver fibrosis.
• To assess the efficacy of Rosiglitazone (RGZ)-loaded perfluoropropane (PFP)-based lipid nanoparticles (LNPs) functionalized with Arg-Gly-Asp (RGD) peptides (RGZ/PFP@LNP-RGD) in vitro and in vivo.
• To investigate the potential of this system for enhanced drug targeting, controlled release, and reduced systemic toxicity.

Main Methods:

• Encapsulation of RGZ within PFP-based LNPs functionalized with RGD peptides for targeted delivery to aHSCs.
• Incorporation of PFP as an ultrasound-responsive agent for controlled drug release.
• In vitro evaluation of RGZ/PFP@LNP-RGD on fibrosis marker expression and HSC activation.
• In vivo assessment of RGZ/PFP@LNP-RGD combined with ultrasound in a liver fibrosis model.

Main Results:

• RGZ/PFP@LNP-RGD treatment reduced key fibrosis markers (Col Iα1, α-SMA, TGF-β1) at both protein and mRNA levels in vitro.
• Ultrasound irradiation enhanced RGZ release and HSC activation inhibition.
• In vivo, RGZ/PFP@LNP-RGD with ultrasound significantly reduced liver fibrosis and improved liver function compared to free RGZ.
• Histological and biochemical analyses confirmed reduced fibrosis and liver damage.

Conclusions:

• RGZ/PFP@LNP-RGD represents a promising nanodrug delivery system for liver fibrosis therapy.
• The combination of targeted nanoparticles and ultrasound offers a noninvasive strategy with enhanced efficacy.
• This approach demonstrates potential for improved drug targeting, controlled release, and minimized systemic toxicity in liver fibrosis treatment.