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Synthesis and Transfection Efficiencies of Divalent Ammonium Headgroup Cationic Lipids with Different Hydrophobic Tails

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Abstract

Cationic lipids with amide or carbamate linker and divalent cationic headgroups were synthesized for a transfection study. Sixteen cationic lipids with double acyl or cholesteryl hydrophobic tails and divalent ammonium headgroups were obtained by a solid phase methodology. The structures of the synthesized lipids were characterized by spectroscopic techniques. The DNA binding affinity of the synthetic lipids was confirmed by gel electrophoresis technique. A lipid with non-symmetrical in length hydrophobic tails (lauroyl and stearoyl) demonstrated higher transfection efficiency than the other lipids in the presence of the helper lipid, dioleoylphosphatidylethanolamine (DOPE), when optimized into the HEK293 cell. At 20% of serum, the same lipid showed relative transfection efficiency equal to that of LipofectamineTM 2000 (L2K). The transfection efficiency of the active lipid was also studied with HeLa, PC3, and HC-04 cell lines. Concerning cell viability, the most potent lipid was non-toxic with respect to the HEK293 and HC-04 cells (over 85% survival). The lipid formed particles of around 380 nm in size with zeta potential around 35 mV at 1: 30 DNA/lipid (weight/weight) ratio.

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ACKNOWLEDGMENTS

We thank the Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, and Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University for facilities support.

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Correspondence to W. Radchatawedchakoon.

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FUNDING

This research was financially supported by Mahasarakham University 2015. CT acknowledges the Science Achievement Scholarship of Thailand (SAST) for the scholarship. Partial support was from the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Ministry of Higher Education, Science, Research, and Innovation.

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The work has no studies involving humans or animals as subjects of the study.

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Authors declare they have no conflicts of interest.

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Corresponding author: phone: +66 43 754246; fax: +66 43 754246; e-mail: widchaya.r@msu.ac.th; widchaya@hotmail.com.

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Radchatawedchakoon, W., Niyomtham, N., Thongbamrer, C. et al. Synthesis and Transfection Efficiencies of Divalent Ammonium Headgroup Cationic Lipids with Different Hydrophobic Tails. Russ J Bioorg Chem 46, 417–428 (2020). https://doi.org/10.1134/S1068162020030140

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  • DOI: https://doi.org/10.1134/S1068162020030140

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