Cargando…

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

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 biocomp...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yi-Mei, Zhang, Ji, Liu, Yan-Hong, Guo, Yu, Yu, Xiao-Qi, Huang, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057412/
https://www.ncbi.nlm.nih.gov/pubmed/35515358
http://dx.doi.org/10.1039/d0ra08027f
_version_ 1784697892207853568
author Zhang, Yi-Mei
Zhang, Ji
Liu, Yan-Hong
Guo, Yu
Yu, Xiao-Qi
Huang, Zheng
author_facet Zhang, Yi-Mei
Zhang, Ji
Liu, Yan-Hong
Guo, Yu
Yu, Xiao-Qi
Huang, Zheng
author_sort Zhang, Yi-Mei
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9057412
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-90574122022-05-04 Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery Zhang, Yi-Mei Zhang, Ji Liu, Yan-Hong Guo, Yu Yu, Xiao-Qi Huang, Zheng RSC Adv Chemistry 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. The Royal Society of Chemistry 2020-11-02 /pmc/articles/PMC9057412/ /pubmed/35515358 http://dx.doi.org/10.1039/d0ra08027f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Zhang, Yi-Mei
Zhang, Ji
Liu, Yan-Hong
Guo, Yu
Yu, Xiao-Qi
Huang, Zheng
Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery
title Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery
title_full Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery
title_fullStr Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery
title_full_unstemmed Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery
title_short Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery
title_sort zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057412/
https://www.ncbi.nlm.nih.gov/pubmed/35515358
http://dx.doi.org/10.1039/d0ra08027f
work_keys_str_mv AT zhangyimei zinciicyclencoordinativeamphiphilesforenhancedgenedelivery
AT zhangji zinciicyclencoordinativeamphiphilesforenhancedgenedelivery
AT liuyanhong zinciicyclencoordinativeamphiphilesforenhancedgenedelivery
AT guoyu zinciicyclencoordinativeamphiphilesforenhancedgenedelivery
AT yuxiaoqi zinciicyclencoordinativeamphiphilesforenhancedgenedelivery
AT huangzheng zinciicyclencoordinativeamphiphilesforenhancedgenedelivery