Self-assembled complexes with dual-targeting properties for gene delivery

Abstract

To improve transfection efficiency, HMGB1 with nuclear localization signals and heparin–biotin (HB) with biotin moieties for cell targeting were used to prepare PAMAM/DNA/HMGB1/HB complexes with dual-targeting properties through self-assembly. For comparison, PAMAM/DNA, PAMAM/DNA/HMGB1 and PAMAM/DNA/HB complexes were also prepared. The self-assembled complexes were characterized by agarose gel electrophoresis and particle size analysis. All complexes exhibit mean sizes less than 150 nm. The in vitro study shows that the presence of HMGB1 facilitates the nuclear transport of DNA, leading to enhanced transfection efficiency. The existence of HB results in decreased cytotoxicity of the complexes and thus improves gene transfection activity. In addition, the complexes containing HB exhibit an enhanced cellular uptake into HeLa cells due to the specific interactions between biotin moieties and biotin receptors on HeLa cells. These results indicate that PAMAM/DNA/HMGB1/HB complexes would have promising potential applications in targeting gene delivery to cancer cells.