Lipoplex size determines lipofection efficiency with or without serum.
In order to identify factors affecting cationic liposome-mediated gene transfer, the relationships were examined among cationic liposome/DNA complex (lipoplex)-cell interactions, lipoplex size and lipoplex-mediated transfection (lipofection) efficiency. It was found that lipofection efficiency was determined mainly by lipoplex size, but not by the extent of lipoplex-cell interactions including binding, uptake or fusion. In addition, it was found that serum affected mainly lipoplex size, but not lipoplex-cell interactions, which effect was the major reason behind the inhibitory effect of serum on lipofection efficiency. It was concluded that, in the presence or absence of serum, lipoplex size is a major factor determining lipofection efficiency. Moreover, in the presence or absence of serum, lipoplex size was found to affect lipofection efficiency by controlling the size of the intracellular vesicles containing lipoplexes after internalization, but not by affecting lipoplex-cell interactions. In addition, large lipoplex particles showed, in general, higher lipofection efficiency than small particles. These results imply that, by controlling lipoplex size, an efficient lipid delivery system may be achieved for in vitro and in vivo gene therapy.
Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan.
Mohamad Radwan
MR
Almofti
Hideyoshi
H
Harashima
Yasuo
Y
Shinohara
Ammar
A
Almofti
Wenhao
W
Li
Hiroshi
H
Kiwada
D002412:Cations; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry; D016895:Culture Media, Serum-Free; D004247:DNA / Q000737:chemistry / Q000493:pharmacokinetics*; D004983:Ethanolamines / Q000737:chemistry; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics; D046911:Macromolecular Substances; D018625:Microscopy, Atomic Force; D009226:Myristates / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods*
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D016895:Culture Media, Serum-Free; D004983:Ethanolamines; D005456:Fluorescent Dyes; D008081:Liposomes; D046911:Macromolecular Substances; D009226:Myristates; C478049:O,O'-detetradecanoyl-N-(alpha-trimethylammonioacetyl)diethanolamine chloride; D010714:Phosphatidylethanolamines; D004247:DNA; D002784:Cholesterol; D008156:Luciferases