Synthesis of Mannosylated Polyethylenimine and Its Potential Application as Cell-Targeting Non-Viral Vector for Gene Therapy

Mannose polyethylenimine with a molecular weight of 25 k (Man-PEI25k) was synthesized via a phenylisothiocyanate bridge using mannopyranosylphenyl isothiocyanate as a coupling reagent, and characterized by H-1 NMR (nuclear magnetic resonance) and FT-IR (Fourier transform infrared spectroscopy) analysis. Spherical nanoparticles were formed with diameters of 80-250 nm when the copolymer was mixed with DNA at various charge ratios of copolymer/DNA (N/P). Gel electrophoresis demonstrated that the DNA had been condensed and retained by the PEI derivates at low N/P ratios. The Man-PEI25k/DNA complexes were less cytotoxic than the PEI complexes with a molecular weight of 25 k (PEI25k) at the same N/P ratio. Laser scan confocal microscopy and flow cytometry confirmed that the Man-PEI25k/DNA complexes gave higher cell uptake efficiency in (Dendritic cells) DC2.4 cells than HeLa cells. The transfection efficiency of Man-PEI25k was higher than that of PEI25k towards DC2.4 cells. These results indicated that Man-PEI25k could be used as a potential DC-targeting non-viral vector for gene therapy.