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Zn(ii)-cyclen complex-based liposomes for gene delivery: the advantage of Zn coordination

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Abstract

The unique properties of 1,4,7,10-tetraazacyclododecane (cyclen) make it not only a suitable polyamine headgroup in cationic lipids for gene delivery, but also a good host molecule for metal coordination. In this study, a series of cyclen-based lipids and their Zn(II)-complexes were synthesized to study the effect of Zn-coordination on the gene transfection. Both the Zn-free and Zn-containing lipids could form nano-sized particles with suitable positive potential to condense and protect DNA from degradation by DNase. More importantly, Zn coordination could significantly reduce the cytotoxicity of the liposomes. Meanwhile, the gene transfection efficiency of the cyclen-based lipids could also be distinctly improved by the Zn-coordination. Mechanistic studies reveal that the Zn-free and Zn-containing liposomes showed similar cellular uptake properties. However, confocal microscopy shows that Zn-containing liposomes may induce more efficient endosomal escape than the Zn-free counterpart, which could be attributed to their much higher pH buffering capacity. This study presents an efficient strategy to enhance the gene transfection efficiency and biocompatibility of cyclen-based cationic lipids.

Graphical abstract: Zn(ii)-cyclen complex-based liposomes for gene delivery: the advantage of Zn coordination

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Publication details

The article was received on 22 Jun 2019, accepted on 31 Aug 2019 and first published on 02 Sep 2019


Article type: Paper
DOI: 10.1039/C9NJ03242H
New J. Chem., 2019, Advance Article

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    Zn(II)-cyclen complex-based liposomes for gene delivery: the advantage of Zn coordination

    Y. Guo, Q. Yu, J. Zhang, H. Yang, Z. Huang and X. Yu, New J. Chem., 2019, Advance Article , DOI: 10.1039/C9NJ03242H

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