Enhancement of transfection activity of lipoplexes by complexation with transferrin-bearing fusogenic polymer-modified liposomes.
We previously developed complexes of lipoplexes containing 3beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-chol) and succinylated poly(glycidol)-modified liposome, which becomes fusogenic under weakly acidic condition, for use as a novel gene delivery system. This study explored the effect of lipoplex structures--the type of cationic lipid and cationic lipid/DNA charge ratio--on the transfection activity of those complexes. Three types of cationic lipid with different polar groups were used for the preparation of lipoplexes: DC-chol, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP), and 3,5-dipentadecyloxybenzamidine (TRX-20) with dimethylamino group, trimethylammonium group, and benzamidine group, respectively. Complexation with the SucPG-modified transferrin-bearing liposomes affected transfection activity of these lipoplexes differently. The TRX-20 lipoplexes exhibited the most marked enhancement of transfection activity upon complexation with the SucPG-modified liposomes among these lipoplexes. The cationic lipid/DNA charge ratio of the lipoplex and the amount of the transferrin-bearing SucPG-modified liposomes associated to the lipoplex also affected the transfection activity of the resultant complexes. Highly potent gene vectors were obtained by adjusting these factors.
Sakaguchi
Naoki
N
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan.
Kojima
Chie
C
Harada
Atsushi
A
Koiwai
Kazunori
K
Shimizu
Kazuhiro
K
Emi
Nobuhiko
N
Kono
Kenji
K
D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D011108:Polymers / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends; D014162:Transfection / Q000379:methods*; D014168:Transferrin / Q000737:chemistry*
D008081:Liposomes; D011108:Polymers; D011993:Recombinant Fusion Proteins; D014168:Transferrin; D008156:Luciferases