Macrophage-Targeting Gene Delivery Using a Micelle Composed of Mannose-Modified Lipid with Triazole Ring and Dioleoyl Trimethylammonium Propane.
Gene carriers with cell specific ligand molecules are needed for the treatment of several diseases. Mannose is known to be recognized and incorporated into the cells through mannose recognition lectins that are exclusively expressed on macrophages. In this study, we synthesized two types of mannose-modified lipids with different stereoisomer (α-mannose and β-mannose). To make a complex with plasmid DNA (pDNA), termed "lipoplex," we prepared a two-component micelle made from cationic lipid; dioleoyltrimethylammoniumpropane (DOTAP); and mannose-modified lipid (D/α-Man or D/β-Man). The prepared D/α-Man lipoplexes were able to bind to one of the α-mannose lectins concanavalin A (ConA) immobilized on gold substrate in the quartz-crystal microbalance sensor cell. D/β-Man lipoplexes did not show any frequency changes. These results indicate that the mannose residues were exposed on the lipoplexes, leading to not only the binding to ConA but also the prevention of nonspecific interactions with proteins. Both lipoplexes showed high transfection efficiencies to RAW264.7 cells which have several kinds of mannose lectins. This delivery system to macrophages may overcome the problems for gene therapy and may be used for the treatment of immune diseases involved in macrophages.
Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
Ichiki
I
Fukuda
Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
Shinichi
S
Mochizuki
Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan ; NexTEP, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
Kazuo
K
Sakurai
D000818:Animals; D002412:Cations; D002460:Cell Line; D003208:Concanavalin A / Q000737:chemistry; D004247:DNA / Q000032:analysis; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006046:Gold / Q000737:chemistry; D008027:Light; D008055:Lipids / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D008823:Micelles; D010957:Plasmids / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D012542:Scattering, Radiation; D014162:Transfection; D014230:Triazoles / Q000737:chemistry*
D002412:Cations; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D008823:Micelles; D000644:Quaternary Ammonium Compounds; D014230:Triazoles; D003208:Concanavalin A; D006046:Gold; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; D008358:Mannose