Abstract
New uncharged gemini-amphiphiles have been synthesized. A series of cationic liposomes based on the polycationic amphiphile 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride (2X3), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and uncharged gemini-amphiphiles that contain short hydrophobic and long hydrophilic spacers have been prepared. The physicochemical characteristics, cytotoxicity, and transfection activity of cationic liposomes have been studied. Cationic liposomes that include 10% (mol) of a uncharged gemini-amphiphile with the oligooxymethylene spacer have formed small complexes with plasmid DNA and efficiently delivered it into eukaryotic cells.
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Funding
The work was supported by the Russian Foundation of Basic Research (grants nos. 18-33-00589 and 18-29-08009). E.V. Shmendel was funded by the president of the Russian Federation fellowship [1199.2018.4].
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Abbreviations: 2X3, 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride; DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; NA, nucleic acids; PI, polydispersity index; IC50, concentration of liposomes provided 50% inhibition of the cell growth; PEG, polyethylene glycol; NMR, nuclear magnetic resonance; EGFP, enhanced green fluorescent protein; FBS, fetal bovine serum; PBS, phosphate buffered saline, pH 7.6; siRNA, short interfering RNA; pDNA, plasmid DNA.
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Shmendel, E.V., Bakhareva, S.A., Makarova, D.M. et al. Uncharged Gemini-Amphiphiles as Components of Cationic Liposomes for Delivery of Nucleic Acids. Russ J Bioorg Chem 46, 1250–1260 (2020). https://doi.org/10.1134/S106816202006031X
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DOI: https://doi.org/10.1134/S106816202006031X