Enhanced gene transfection in macrophages using mannosylated cationic liposome-polyethylenimine-plasmid DNA complexes.

We have previously reported that plasmid DNA and cholesten-5-yloxy-N-(4-[(1-imino-2-beta-D-thiomannosylethyl)amino]butyl) formamide(Man-C4-Chol)/dioleoylphosphatidylethano-lamine(DOPE)(6:4) liposome complexes (DNA/Man-complexes) exhibit efficient gene transfection in macrophages via mannose receptor-mediated endocytosis. To further enhance gene transfetion, polyethylenimine (PEI) was incorporated into this liposome complex (DNA/Man-PEI-complexes), noticing a pH-buffering capacity in endosomes and DNA-condensing activity of PEI. In mouse peritoneal macrophages, the uptake and transfection activity of DNA/Man-PEI-complexes were 2-times and 6-times higher than those of DNA/Man-complexes, respectively. Furthermore, the presence of 1 mg/ml mannan significantly inhibited both the uptake and transfection efficiency of DNA/Man-PEI-complexes. These results suggested that the newly developed multifunctional DNA/Man-PEI-complexes exhibit highly improved gene transfection in macrophages via mannose receptor-mediated endocytosis.