Anchor-dependent lipofection with non-glycerol based cytofectins containing single 2-hydroxyethyl head groups.
Detailed structure-activity investigations aimed at probing the anchor chain length dependency for glycerol-based lipofectins have been reported previously. Herein, we report on the first detailed investigation on the anchor-dependent transfection biology of non-glycerol based simple monocationic cytofectins containing single 2-hydroxyethyl head group functionality using 11 new structural analogs of our previously published first generation of non-glycerol based transfection lipids (lipids 1-11). The C-14 and C-16 analogs of DOMHAC (lipids 4 and 5, respectively) were found to be remarkably efficient in transfecting COS-1 cells. In addition, the present anchor-dependency investigation also revealed that the C-14 analog of DOHEMAB (lipid 10) is significantly efficient in transfecting both COS-1 and NIH3T3 cells. Our results also indicate that too strong lipid-DNA interactions might result in weaker transfection for non-glycerol based cationic lipids. In summary, the anchor-dependence investigations presented here convincingly demonstrate that non-glycerol based cationic lipids containing a single hydroxyethyl head group and hydrophobic C-14 or C-16 anchors are promising non-toxic cationic transfection lipids for future use in liposomal gene delivery.
Venkata Srilakshmi
Gollapudi
G
Division of Lipid Science and Technology, Indian Institute of Chemical Technology, Hyderabad, India.
Sen
Joyeeta
J
Chaudhuri
Arabinda
A
Ramadas
Yerramsetti
Y
Madhusudhana Rao
Nalam
N
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002411:Cation Exchange Resins / Q000737:chemistry*; D004337:Drug Carriers; D015316:Genetic Therapy; D005990:Glycerol / Q000737:chemistry; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D008081:Liposomes; D051379:Mice; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods
D002411:Cation Exchange Resins; D004337:Drug Carriers; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; C451503:N,N-di-(O-hexadecanoyl)hydroxyethyl-N-hydroxyethyl-N-methylammonium; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C020888:1,2-dielaidoylphosphatidylethanolamine; D005990:Glycerol