Abstract
In this study, a series of Zn(II)-dipicolylamine (Zn-DPA) based cationic lipids bearing different hydrophobic tails (long chains, α-tocopherol, cholesterol or diosgenin) were synthesized. Structure–activity relationship (SAR) of these lipids was studied in detail by investigating the effects of several structural aspects including the type of hydrophobic tails, the chain length and saturation degree. In addition, several assays were used to study their interactions with plasmid DNA, and results reveal that these lipids could condense DNA into nanosized particles with appropriate size and zeta-potentials. MTT-based cell viability assays showed that lipoplexes 5 had low cytotoxicity. The in vitro gene transfection studies showed the hydrophobic tails clearly affected the TE, and hexadecanol-containing lipid 5b gives the best TE, which was 2.2 times higher than bPEI 25k in the presence of 10% serum. The results not only demonstrate that these lipids might be promising non-viral gene vectors, but also afford us clues for further optimization of lipidic gene delivery materials.
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Acknowledgements
This work was financially supported by the Science and Technology Department of Sichuan Province (No. 2015JY0115) and the Fundamental Research Funds for the Central Universities, Southwest University for Nationalities (No. 2016NZYZQ66). Qiang Liu thanks Prof. Xiao-Qi Yu and Prof. Ji Zhang from the Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University for their support.
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Su, RC., Liu, Q., Yi, WJ. et al. Zn(II)-dipicolylamine-based metallo-lipids as novel non-viral gene vectors. J Biol Inorg Chem 22, 867–879 (2017). https://doi.org/10.1007/s00775-017-1465-0
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DOI: https://doi.org/10.1007/s00775-017-1465-0