A hepatic-targeted glycogen-based nano-platform enables efficient CTGF silencing and attenuates liver fibrosis

Min Gao1, Zhongtao Wen1, Xinyuan Zhang1

  • 1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214000, People's Republic of China.

Nanotechnology
|February 9, 2026
PubMed

Insights

A novel nanoparticle system effectively delivers gene-silencing therapy to treat liver fibrosis. This approach enhances therapeutic efficacy and biosafety for chronic liver disease management.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Hepatology

Background:

  • Liver fibrosis is a precursor to cirrhosis, posing significant clinical challenges due to limited treatment options.
  • Current gene silencing therapies for liver fibrosis face hurdles in delivery, stability, and targeting.
  • Developing effective delivery systems is crucial for advancing gene silencing therapies.

Purpose of the Study:

  • To develop a targeted nanoparticle system for efficient delivery of siRNA to treat liver fibrosis.
  • To engineer a biocompatible and stable nanocarrier for enhanced gene silencing efficacy.
  • To evaluate the therapeutic potential of the novel system in preclinical models of liver fibrosis.

Main Methods:

  • A lactobionic acid-modified aminated glycogen (Lac-AGly) nanoparticle system was synthesized using natural glycogen.
  • The nanoparticles were loaded with siRNA targeting connective tissue growth factor (CTGF) to create Lac-AGly/siCTGF nanocomplexes.
  • Nanoparticle characterization included morphology, size, and zeta potential analysis.
  • In vivo studies assessed the efficacy of Lac-AGly/siCTGF in attenuating liver fibrosis.

Main Results:

  • Lac-AGly nanoparticles demonstrated efficient siRNA binding and selective hepatocyte targeting via ASGPR.
  • The Lac-AGly/siCTGF nanocomplexes showed uniform spherical morphology (247.2 ± 8.8 nm) and positive zeta potential (28.5 ± 3.8 mV).
  • In vivo administration significantly reduced liver fibrosis, decreasing collagen-positive areas from 14.3% to 3.1%.
  • The system exhibited improved serum stability and favorable biosafety profiles.

Conclusions:

  • The Lac-AGly/siCTGF nanoparticle system offers a promising, biocompatible, and stable platform for targeted siRNA delivery.
  • This novel strategy significantly enhances gene silencing efficacy for precise molecular intervention in liver fibrosis.
  • The developed system represents a translatable approach for managing chronic liver diseases and preventing cirrhosis.

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