Efficient serum-resistant lipopolyplexes targeted to the folate receptor

Area of Science:

• Biotechnology
• Gene Therapy
• Nanomedicine

Background:

• Gene delivery systems face challenges with serum inhibition and cytotoxicity.
• Targeted delivery enhances therapeutic efficacy and reduces off-target effects.

Purpose of the Study:

• To develop and evaluate a novel targeted lipopolyplex (Fol-LPP) for enhanced gene delivery.
• To assess the efficacy and specificity of Fol-LPP in high-serum environments.
• To investigate the potential of Fol-LPP for therapeutic gene delivery in vitro and in vivo.

Main Methods:

• Lipopolyplexes (LPPs) were formulated using polyethylenimine (PEI), DOTAP/Chol liposomes, and folic acid (FA).
• Plasmid DNA encoding luciferase (pCMVLuc) or interleukin-12 (pCMVIL-12) was complexed with LPPs.
• Transfection efficiency was evaluated in HeLa and B16-F10 cells under 60% FBS conditions.
• Folate receptor (FR)-mediated specificity was confirmed using FR-deficient HepG2 cells.

Main Results:

• Fol-LPP demonstrated efficient gene transfection in HeLa and B16-F10 cells, even with 60% FBS.
• Folic acid conjugation significantly enhanced IL-12 gene transfection activity.
• No significant cytotoxicity was observed with the Fol-LPP formulation.
• Specificity of FR-mediated gene transfer was confirmed in HepG2 cells.

Conclusions:

• Fol-LPP represents an efficient, simple, and non-toxic gene delivery system.
• The formulation overcomes serum inhibition, improving therapeutic gene delivery.
• Fol-LPP shows significant potential for both in vitro and in vivo applications in gene therapy.