Specific and efficient gene delivery mediated by an asialofetuin-associated nanosystem

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Oncology

Background:

• Hepatocellular carcinoma (HCC) remains a significant global health challenge.
• Gene therapy presents a promising avenue for HCC treatment, but efficient and specific delivery remains a hurdle.
• Targeting overexpressed receptors on HCC cells is a key strategy for improving gene delivery efficacy.

Purpose of the Study:

• To develop and evaluate a novel gene delivery nanosystem for hepatocellular carcinoma (HCC).
• To utilize asialofetuin (ASF), a ligand for the asialoglycoprotein receptor (ASGP-R), for targeted delivery to HCC cells.
• To assess the specificity and efficiency of the ASF-lipoplex nanosystem in vitro and in vivo.

Main Methods:

• Fabrication of cationic liposomes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine and cholesterol, complexed with asialofetuin (ASF).
• Evaluation of ASF-lipoplex transfection efficiency and cellular uptake in HCC cells, comparing with a commercial formulation.
• Assessment of ASF-lipoplex activity in an animal model of HCC and investigation of the role of ASGP-R interaction using galactose and endocytosis inhibitors.

Main Results:

• Association of ASF to lipoplexes significantly enhanced biological activity and transfection efficiency in HCC cells.
• The novel ASF-lipoplex nanosystem demonstrated substantially higher transfection activity compared to a commercial formulation.
• Cellular uptake and biological activity were significantly reduced by high galactose concentrations and endocytosis inhibitors, confirming specific ASGP-R interaction.
• Physicochemical properties of the nanosystem supported the specific interaction with ASGP-R.

Conclusions:

• Novel ASF-lipoplexes specifically and efficiently deliver genetic material into HCC cells.
• The developed nanosystem shows significant potential as a targeted gene therapy for hepatocellular carcinoma.
• ASF-mediated targeting via ASGP-R interaction is a viable strategy for enhancing gene delivery in HCC.