Synthesis, and Characterization, and Evaluation of Cellular Effects of the FOL‐PEG‐g‐PEI‐GAL Nanoparticles as a Potential Non‐Viral Vector for Gene Delivery

Abstract

In this manuscript, we synthesized the potential non viral vector for gene delivery with proper transfection efficiency and low cytotoxicity. Polyethylenimine (PEI) is a well‐known cationic polymer which has high positive surface charge for condensing plasmid DNA. However; it is highly cytotoxic in many cell lines because of the high surface charge, non‐biodegradability and non‐biocompatibility. To enhance PEI biodegradability, the graft copolymer “PEG‐g‐PEI” was synthesized. To target cancer liver cells, two targeting ligands folic acid and galactose (lactobionic acid) which are over expressed on human hepatocyte carcinoma were attached to graft copolymer and “FOL‐PEG‐g‐PEI‐GAL” copolymer was synthesized. Composition of this grafted copolymer was characterized using 1H‐NMR and FTIR spectra. The molecular weight and zeta potential of this copolymer was compared to PEI. The particle size and zeta potential of FOL‐PEG‐g‐PEI‐GAL/DNA complexes at various N/P ratio were measured using dynamic light scattering (DLS). Cytotoxicity of the copolymer was also studied in cultured HepG2 human hepatoblastoma cell line. The FOL‐PEG‐g‐PEI‐GAL/DNA complexes at various N/P ratios exhibited no cytotoxicity in HepG2 cell line compared to PEI 25K as a control. The novel copolymer showed enhanced biodegradability in physiological conditions in compared with PEI and targeted cultured HepG2 cells. More importantly, significant transfection efficiency was exhibited in cancer liver cells. Together, our results showed that “FOL‐PEG‐g‐PEI‐GAL” nanoparticals could be considered as a useful non‐viral vector for targeted gene delivery.