Design, synthesis, and in vitro gene delivery efficacies of novel cholesterol-based gemini cationic lipids and their serum compatibility: a structure-activity investigation.
Five cholesterol-based gemini cationic lipids, which differ in the length of the spacer [-(CH2)n-] chain between the head groups, have been synthesized. These lipids are useful as nonviral gene delivery agents, and all cholesterol-based gemini lipids (2a-2e) are better transfecting agents than their monomeric lipid counterpart 1. Transfection efficiency of all the gemini lipids except lipid 2a [-(CH2)3-] was maintained even when the serum was present during the transfection conditions as compared to the monomeric lipid 1, with which a dramatic decrease in transfection efficiency was observed. With the increase in spacer chain length from propanediyl [-(CH2)3-] to pentanediyl [-(CH2)5-], transfection efficiency increased both in the absence and presence of serum. However, transfection efficiency decreased with further increase in the length from the pentanediyl [-(CH2)5-] to the dodecanediyl [-(CH2)12-] spacer. Among these gemini lipids 2c showed the highest transfection activity, which was also greater than that of the commercially available formulation.
Bajaj
Avinash
A
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India.
Kondiah
Paturu
P
Bhattacharya
Santanu
S
D002412:Cations; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000008:administration & dosage; D015195:Drug Design; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000633:toxicity; D010714:Phosphatidylethanolamines / Q000737:chemistry; D044967:Serum; D013329:Structure-Activity Relationship; D014162:Transfection
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D008081:Liposomes; D010714:Phosphatidylethanolamines; D049452:Green Fluorescent Proteins; D004247:DNA; D002784:Cholesterol