A biocleavable pullulan-based vector via ATRP for liver cell-targeting gene delivery

Area of Science:

• Biomaterials Science
• Gene Therapy
• Polymer Chemistry

Background:

• Pullulan's liver specificity makes it ideal for biomedical applications.
• Efficient and safe gene delivery vectors are crucial for therapeutic development.

Purpose of the Study:

• To design and synthesize a novel, biocompatible, and liver-targeting gene delivery vector based on pullulan.
• To evaluate the in vitro gene transfection efficiency, cellular uptake, and hemocompatibility of the developed vector.

Main Methods:

• Synthesis of a biocleavable pullulan-based gene vector (PuPGEA) using atom transfer radical polymerization (ATRP).
• Functionalization of pullulan with reduction-sensitive disulfide-linked poly(glycidyl methacrylate) (PGMA) side chains, further modified with ethanolamine (EA).
• In vitro evaluation of gene transfection efficiency, cellular uptake in HepG2 and Hella cell lines, and hemocompatibility compared to polyethylenimine (PEI).

Main Results:

• The synthesized PuPGEA vectors demonstrated efficient liver cell targeting, with significantly higher transfection efficiency and cellular uptake in HepG2 cells compared to Hella cells.
• The study identified the involvement of the asialoglycoprotein receptor in the hepatocyte transfection process.
• PuPGEA vectors exhibited excellent hemocompatibility, showing no significant hemolysis, unlike the control PEI.

Conclusions:

• The developed biocleavable, comb-shaped PuPGEA vectors are effective for liver cell-targeting gene delivery.
• Grafting bioreducible polycation side chains onto a pullulan backbone creates a promising hemocompatible, polysaccharide-based gene delivery system.
• PuPGEA offers a safe and efficient alternative to conventional gene delivery vectors for liver-specific applications.