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.
Sato
A
A
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Kawakami
S
S
Yamada
M
M
Yamashita
F
F
Hashida
M
M
D000818:Animals; D002478:Cells, Cultured; D008081:Liposomes / Q000138:chemical synthesis*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014162:Transfection
D008081:Liposomes