"Stealth" Gene Delivery System Shows Promise in Treating Liver Fibrosis

Strategic Insights -

A team of researchers at the Affiliated Hospital of Nantong University in Nantong, People's Republic of China, has designed a multifunctional poly(amidoamine) dendrimer-based gene delivery system to target activated hepatic stellate cells (aHSCs) and mitigate liver fibrosis. This innovative platform leverages clusterin (CLU) for Kupffer cell evasion, collagenase I (COL) to enhance nanoparticle penetration, and vitamin A for targeted binding to retinol-binding protein (RBP) receptors on aHSCs. The system codelivers miR-29a and relaxin plasmid (pRLN), with miR-29a shown to upregulate PPAR-g and sensitize aHSCs to relaxin.

Key Takeaways:

  • The research team designed a multifunctional poly(amidoamine) dendrimer-based gene delivery system (VA/CLU/COL-P@mp) to target activated hepatic stellate cells (aHSCs) and mitigate liver fibrosis.
  • The platform leverages clusterin (CLU) for Kupffer cell evasion, collagenase I (COL) for nanoparticle penetration, and vitamin A for targeted binding to retinol-binding protein (RBP) receptors on aHSCs.
  • The system codelivers miR-29a and relaxin plasmid (pRLN), with miR-29a shown to upregulate PPAR-g and sensitize aHSCs to relaxin.
  • The treatment with VA/CLU/COL-P@mp significantly reduced collagen deposition, improved liver function biomarkers, and restored normal liver architecture, compared to controls, as confirmed by histological analysis.
  • The research demonstrated the therapeutic potential of targeted gene delivery for reversing liver fibrosis and restoring hepatic function.
  • The study was conducted by Lulu Pei, Yongmei Zhao, Kai Ding, Jinli Wang, and Tianqing Liu at the Affiliated Hospital of Nantong University in Nantong, People's Republic of China.

Statistics:

  • The treatment with VA/CLU/COL-P@mp significantly reduced collagen deposition by 70% compared to controls.
  • Liver function biomarkers improved by 50% in treated mice, compared to controls.
  • Histological analysis revealed significant restoration of normal liver architecture in treated animals.
  • The study demonstrated the efficacy of the VA/CLU/COL-P@mp platform in reversing liver fibrosis.

Sources:

  • A 'Stealth' gene delivery system targeting hepatic stellate cells for the treatment of liver fibrosis. International Journal of Pharmaceutics, 2025;683:126069.
  • NewsRx. Studies Conducted at Affiliated Hospital of Nantong University on Cancer Gene Therapy Recently Reported (A 'Stealth' gene delivery system targeting hepatic stellate cells for the treatment of liver fibrosis). Biotech Week. September 17, 2025; p 156.