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Replacement of quaternary ammonium headgroup by tri-ornithine in cationic lipid for the improvement of gene delivery in vitro and in vivo

Abstract

Headgroups in cationic lipids play very important roles in determining transfection efficiency and toxicity in gene delivery. To better understand the influence of headgroups on gene delivery, a tri-peptide-based lipid was synthesized, wherein the usual quaternary ammonium was replaced by a tri-peptide. Though both the tri-peptide-based lipid (DAO3) and the quaternary ammonium-based lipid (DDCTMA) successfully mediated gene transfection, DAO3 was superior over DDCTMA in both in vitro and in vivo studies. Following their preparation into liposomes, the particle size, Zeta potential, and DNA-binding capacity of liposomes and lipoplexes were characterized to evaluate the efficiency of DAO3 as compared to DDCTMA with regard to gene interactions. The expression of luciferase of pDNA mediated by DAO3 was 2-fold greater than DDCTMA in Hep-2 cells, and DAO3/siRNA lipoplexes could silence about 60% luciferase in A549 cancer cells expressing firefly luciferase. DAO3/Luc-siRNA treatment exhibited 3-fold the efficiency of DDCTMA/Luc-siRNA in terms of in vivo luciferase RNAi with the bare density ratio of 0.54 at 48 h. Furthermore, DAO3 could mediate IGF-1R siRNA to inhibit tumor growth through silencing the expression of IGF-1R protein, whereas DDCTMA showed nearly no effects. Most importantly, DAO3 had no obvious toxicity in vitro and in vivo, due to the biocompatibility of the peptide headgroups. In conclusion, these results demonstrated that the replacement of quaternary ammonium headgroup by tri-ornithine may increase transfection efficiency and decrease toxicity.

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Publication details

The article was received on 17 Jul 2017, accepted on 13 Sep 2017 and first published on 13 Sep 2017


Article type: Paper
DOI: 10.1039/C7TB01915G
Citation: J. Mater. Chem. B, 2017, Accepted Manuscript
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    Replacement of quaternary ammonium headgroup by tri-ornithine in cationic lipid for the improvement of gene delivery in vitro and in vivo

    Y. Zhao, Y. Piao, C. Zhang, Y. Jiang, A. Liu, S. Cui, D. Zhi, Y. Zhen and S. zhang, J. Mater. Chem. B, 2017, Accepted Manuscript , DOI: 10.1039/C7TB01915G

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