Issue 65, 2020

Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery

Abstract

In this study, we developed coordinative amphiphiles for use as novel non-viral DNA vectors. As a modification of a conventional cationic lipid structure, we replaced the cationic head with a zinc(II)-1,4,7,10-tetraazacyclododecane (Zn-cyclen) complex as a phosphate-directing group, and used biocompatible skeletons (α-tocopherol or cholesterol) as hydrophobic tails. The structure-activity relationship (SAR) was systematically investigated to study the effect of Zn-coordination on the gene transfection between cyclen-based traditional head-tail lipids and Zn(II)-cyclen coordinative amphiphiles. The results reveal that both Zn-free lipids and Zn-containing amphiphiles could condense DNA into nano-sized particles with appropriate size and zeta-potentials. Agarose gel retardation assay and MTS-based cell viability assays demonstrated that the Zn(II)-cyclen complex exhibited slightly lower DNA binding ability and much lower cytotoxicity compared to liposome analogues, respectively. Most importantly, in vitro transfection studies showed that the coordination of zinc(II) to cyclen may dramatically increase the transfection efficiency of the conventional cationic lipid, and α-tocopherol-containing coordinative amphiphile Zn-Cyc-Toc gives the best transfection efficiency, which was enhanced 24.4 times after coordination and was 6.1 times higher than commercial transfection reagent lipofectamine 2000. Mechanism studies confirmed that the DNA complex formed from Zn-Cyc-Toc might induce higher cellular uptake and better endosomal escape ability than the lipoplexes formed from Zn-free lipid Cyc-Toc. This study not only demonstrates that these coordinative amphiphiles might be promising non-viral gene vectors, but also presents a novel strategy to enhance the gene transfection efficiency and biocompatibility of cyclen-based cationic lipids.

Graphical abstract: Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery

Article information

Article type
Paper
Submitted
20 Sept. 2020
Accepted
23 Okt. 2020
First published
02 Nov. 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 39842-39853

Zinc(II)-cyclen coordinative amphiphiles for enhanced gene delivery

Y. Zhang, J. Zhang, Y. Liu, Y. Guo, X. Yu and Z. Huang, RSC Adv., 2020, 10, 39842 DOI: 10.1039/D0RA08027F

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements