title: Cholesterol derived cationic lipids as potential non-viral gene delivery vectors and their serum compatibility.
abstract: Cholesterol derivatives M1-M6 as synthetic cationic lipids were designed and the biological evaluation of the cationic liposomes based on them as non-viral gene delivery vectors were described. Plasmid pEGFP-N1, used as model gene, was transferred into 293T cells by cationic liposomes formed with M1-M6 and transfection efficiency and GFP expression were tested. Cationic liposomes prepared with cationic lipids M1-M6 exhibited good transfection activity, and the transfection activity was parallel (M2 and M4) or superior (M1 and M6) to that of DC-Chol derived from the same backbone. Among them, the transfection efficiency of cationic lipid M6 was parallel to that of the commercially available Lipofectamine2000. The optimal formulation of M1 and M6 were found to be at a mol ratio of 1:0.5 for cationic lipid/DOPE, and at a N/P charge mol ratio of 3:1 for liposome/DNA. Under optimized conditions, the efficiency of M1 and M6 is greater than that of all the tested commercial liposomes DC-Chol and Lipofectamine2000, even in the presence of serum. The results indicated that M1 and M6 exhibited low cytotoxicity, good serum compatibility and efficient transfection performance, having the potential of being excellent non-viral vectors for gene delivery.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China; Department of Pharmacy, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Meng-Lei
authors.initials: ML
authors.lastname: Huan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wan
authors.affiliation: Innovative Experimental College, Northwest A&F University, Yangling 712100, China.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Hou
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xi-Xi
authors.initials: XX
authors.lastname: Ma
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Jia
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. Electronic address: blezhang@fmmu.edu.cn.
authors.forename: Bang-Le
authors.initials: BL
authors.lastname: Zhang
mesh_terms: D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D044967:Serum / Q000737:chemistry; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods
chemical_list: D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D049452:Green Fluorescent Proteins; C094877:dioleoyl phosphatidylethanolamine; D002784:Cholesterol
keywords: Cationic liposome; Cytotoxicity; Non-viral vector; Serum compatibility; Transfection activity