Novel gene delivery systems: complexes of fusigenic polymer-modified liposomes and lipoplexes.
We have previously developed the succinylated poly(glycidol)-modified liposome which becomes fusigenic under weakly acidic condition. In this report, we describe that complexation of this pH-sensitive, fusigenic liposome with a lipoplex consisting of 3beta-(N-(N',N'-dimethylaminoethane) carbamoyl)cholesterol, dioleoylphosphatidylethanolamine and plasmid DNA gives efficient gene delivery systems. In this study, we prepared the complexes, which are termed SucPG-complexes, with a positively or negatively charged surface by mixing the lipoplex with varying amounts of the SucPG-modified liposomes. The positively charged SucPG-complexes either bearing or not bearing a cell-specific ligand, transferrin, could transfect HeLa cells efficiently. In contrast, the negatively charged complexes hardly transfected the cells when transferrin was not conjugated to them. However, the negatively charged SucPG complexes bearing transferrin exhibited high transfection ability against HeLa and K562 cells, indicating that this gene delivery was achieved through their binding to the cellular receptors. These transferrin-attached, negatively charged complexes retained the high transfection ability in the presence of serum. Thus, this negatively charged complex may be useful as nonviral vectors in vivo.
Kono
K
K
Department of Applied Materials Science, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan.
Torikoshi
Y
Y
Mitsutomi
M
M
Itoh
T
T
Emi
N
N
Yanagie
H
H
Takagishi
T
T
D001769:Blood; D016923:Cell Death; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008081:Liposomes / Q000737:chemistry*; D010957:Plasmids; D014162:Transfection / Q000379:methods*; D014168:Transferrin / Q000378:metabolism
D008024:Ligands; D008081:Liposomes; D014168:Transferrin