Cholic acid modified 2 kDa polyethylenimine as efficient transfection agent.

Area of Science:

• Biomaterials Science
• Gene Therapy
• Polymer Chemistry

Background:

• Gene delivery systems are crucial for genetic therapies.
• Polyethylenimines (PEI) are widely studied non-viral gene vectors.
• Improving PEI's safety and efficacy remains a key challenge.

Purpose of the Study:

• To synthesize novel lipopolymers by conjugating cholic acid (ChA) to PEI and polyallylamine (PAA).
• To evaluate these lipopolymers as effective gene delivery systems.
• To investigate the impact of ChA conjugation on polymer properties and gene transfection efficiency.

Main Methods:

• Synthesis of lipopolymers via N-acylation of PEI (2 and 25 kDa) and PAA (15 kDa) with cholic acid.
• Characterization of grafting ratio and plasmid DNA (pDNA) binding capability.
• Assessment of cytotoxicity and transfection efficiency in 293T cells and mesenchymal stem cells.

Main Results:

• Controlled ChA substitution was achieved, varying linearly with the feed ratio.
• ChA conjugation significantly impacted pDNA binding for 2 kDa PEI but not higher MW polymers.
• Cytotoxicity was reduced for higher MW polymers, while transfection efficiency improved for 2 kDa PEI.

Conclusions:

• Cholic acid is a suitable substituent for enhancing the gene delivery capabilities of low MW PEIs.
• Lipopolymer modification offers a strategy to improve non-viral gene vector performance.
• This approach holds potential for developing safer and more effective gene therapy vectors.