Structural, biocomplexation and gene delivery properties of hydroxyethylated gemini surfactants with varied spacer length
2016
Zakharova, Lucia Ya | Gabdrakhmanov, Dinar R. | Ibragimova, Alsu R. | Vasilieva, Elmira A. | Nizameev, Irek R. | Kadirov, Marsil K. | Ermakova, Elena A. | Gogoleva, Natalia E. | Faizullin, Dzhigangir A. | Pokrovsky, Andrey G. | Korobeynikov, Vladislav A. | Cheresiz, Sergey V. | Zuev, Yuriy F.
Gemini surfactants with hexadecyl tails and hydroxyethylated head groups bridged with tetramethylene (G4), hexamethylene (G6) and dodecamethylene (G12) spacers were shown to self-assemble at the lower critical micelle concentration compared to their conventional m-s-m analogs. The lipoplex formation and the plasmid DNA transfer into different kinds of host cells were studied. In the case of eukaryotic cells, high transfection efficacy has been demonstrated for DNA–gemini complexes, which increased as follows: G6<G4<G12. Different activity series, i.e., G6>G4>G12 has been obtained in the case of transformation of bacterial cells with plasmid DNA–gemini complexes, mediated by electroporation technique. Solely G6 shows transformation efficacy exceeding the control result (uncomplexed DNA), while the inhibitory effect occurs for G4 and G12. Analysis of physico-chemical features of single surfactants and lipoplexes shows that compaction and condensation effects change as follows: G6<G4≤G12, i.e., agree with the order of transfection efficacy, which is supported by membrane tropic properties of G12. On the other hand, gel retardation assay and docking study testify low electrostatic affinity in G12/DNA pair, thereby indicating that hydrophobic effect probably plays important role in the lipoplex formation. Two factors are assumed to be responsible for the inhibition effect of gemini in the case of transformation of bacterial cells. They are (i) an unfavorable influence of cationic surfactants on the electroporation procedure due to depressing the electrophoretic effect; and (ii) antibacterial activity of cationic surfactants that may cause the disruption of integrity of cell membranes.
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