Correlation between structure and transfection efficiency: a study of DC-Chol--DOPE/DNA complexes.
The supramolecular structural nature of some cationic liposomes-DNA complexes, currently used as vehicles in non-viral gene delivery, has been elucidated by recent X-ray diffraction experiments. The relationship between the chemico-physical properties of these self-assembled structures and their transfection efficiency is extensively studied. Here we report a first comprehensive structural study by using energy dispersive X-ray diffraction, of the complex DC-Chol--DOPE/DNA (3beta[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol dioleoylphosphatidylethanolamine/DNA), which has been classified as one of the most effective in in-vivo experiments. Our results show that DC-Chol--DOPE/DNA lipoplexes have a columnar inverted hexagonal structure, which is not influenced by the cationic liposome/DNA charge ratio. The transfection efficiency of C6 rat glioma cells by DC-Chol--DOPE/DNA lipoplexes and the toxicity of lipoplexes to cells are dramatically affected by cationic liposome/DNA weight ratio. It seems therefore that the lipoplex structures have not any influence on transfection efficiency and toxicity in our experimental system.
Congiu
Agostina
A
Dipartimento di Fisica, P.le A. Moro 5, 00185 Rome, Italy. a.congiu@caspur.it
Pozzi
Daniela
D
Esposito
Claudio
C
Castellano
Carlo
C
Mossa
Giuseppe
G
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000633:toxicity; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D005910:Glioma; D008081:Liposomes / Q000737:chemistry*; D008156:Luciferases / Q000378:metabolism; D008956:Models, Chemical; D008970:Molecular Weight; D010714:Phosphatidylethanolamines / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D018675:Toxicity Tests; D014162:Transfection
D004273:DNA, Neoplasm; D008081:Liposomes; D010714:Phosphatidylethanolamines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; C094877:dioleoyl phosphatidylethanolamine; D002784:Cholesterol; D008156:Luciferases