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A novel redox-sensitive polycationic amphiphile ( 2S3 ) with disulphide linkers for nucleic acid delivery was developed. Cationic liposomes formed by 2S3 and the helper lipid DOPE demonstrated effective DNA delivery into HEK293 cells with a maximal transfection activity that is superior than both nonredox-sensitive cationic liposomes and Lipofectamine® 2000 at an N/P ratio of 6/1. Redox-sensitivity was tested by experiments with extracellular glutathione which shown the ability of disulphide linker degradation. Our results suggest that polycationic amphiphile 2S3 is a promising candidate for nucleic acid delivery. [ABSTRACT FROM AUTHOR]

Three novel polycationic gemini amphiphiles with different spacers were developed and evaluated in terms of their physiochemical properties and transfection efficiencies. Cationic liposomes formed by these amphiphiles and the helper lipid DOPE were able to successfully condense DNA, as shown by gel mobility shift and ethidium bromide intercalation assays. Transfection activity of the liposomes was superior to Lipofectamine ® 2000 and was dependent on spacer structure, hydrophobicity, and nucleic acid type (pDNA or siRNA). We demonstrated that the cationic liposomes 2X6/DOPE and 2X7/DOPE are potential non-toxic vehicles for gene delivery. [ABSTRACT FROM AUTHOR]