title: Preparation and gene delivery of alkaline amino acids-based cationic liposomes.
abstract: Cationic lipids 1, 2, and 3, based on hydrophobic cholesterol linked to L-lysine, L-histidine or L-arginine, respectively, were designed and tested as gene delivery vectors. Physicochemical and biological properties of all liposomes and lipoplexes were evaluated, including lipid-DNA interactions, size, morphology, zeta potential, acid-base buffering capability, protection of DNA from DNase I digestion, and cytotoxity. The efficiency of luciferase gene transfection of lipoplexes 1-3 was compared with that of commercial dioleoyl-trimethylammonium propane (DOTAP) and polyethyleneimine (PEI) in 293T cells and HepG2 cells with or without poly(ethylene glycol) PEG stabilizer. The complexation and protection of DNA of liposome 3 was the strongest among the three liposomes. The efficiency of gene transfection of liposomes 1-3 was two-to threefold higher than that of PEI and/or DOTAP in 293T cells. Liposomes 1 and 3 in PEG as stabilizer showed sixfold higher transfection efficiency than that of PEI and/or DOTAP, whereas liposome 2 showed very low transfection efficiency. In HepG2 cells, the transfection efficiency of all the cationic liposomes was much lower than that of DOTAP. In conclusion, lipids 1-3 were efficient and non-toxic gene vectors; the headgroup of cationic lipids and the stabilizer of liposome formulation had an important influence on gene transfection.
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Nie
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.forename: Sanjun
authors.initials: S
authors.lastname: Shi
authors.forename: Kui
authors.initials: K
authors.lastname: Luo
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Junxiao
authors.initials: J
authors.lastname: Yang
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry; D002412:Cations; D002460:Cell Line; D002784:Cholesterol / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008027:Light; D008081:Liposomes / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D012542:Scattering, Radiation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection
chemical_list: D000596:Amino Acids; D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D013778:Tetrazolium Salts; D013844:Thiazoles; D006639:Histidine; D001120:Arginine; D002784:Cholesterol; D008156:Luciferases; D003850:Deoxyribonuclease I; C022616:thiazolyl blue; D008239:Lysine