Effect of the nature of the spacer on gene transfer efficacies of novel thiocholesterol derived gemini lipids in different cell lines: a structure-activity investigation.
A structure-activity investigation was undertaken to see the effect of the nature of the spacer on the gene transfection efficacies of thiocholesterol-derived cationic gemini lipids possessing disulfide linkage between the cationic headgroup and the thiocholesterol moiety. Three gemini cationic lipids possessing hydrophobic flexible (-(CH 2) 5-; 1), hydrophobic rigid (-C 6H 4-; 2), and hydrophilic flexible (-CH 2-CH 2-O-CH 2-CH 2-; 3) spacer segments were synthesized. In HeLa cells, lipid formulations 1 and 2 were found to be more effective as compared to lipid 3 formulation. In HT1080 cell line, the order of transfectability was 3 > 1 > 2. Transfection studies in HeLa and HT1080 cell line also showed 40-50% transfection efficacy in the presence of 10% serum conditions. These formulations were also able to transfect gene across difficult cells like HaCaT. Cytotoxic studies showed the nontoxic nature of these lipid-DNA complexes at different N/P ratios used for transfection studies.
Bajaj
Avinash
A
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India.
Kondaiah
Paturu
P
Bhattacharya
Santanu
S
D002460:Cell Line; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D046529:Microscopy, Electron, Transmission; D013329:Structure-Activity Relationship
D008055:Lipids; D008081:Liposomes; C002297:thiocholesterol; D004247:DNA; D002784:Cholesterol