Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery

Jiankun Yu,1 Jinmin Zhang,1 Haonan Xing,1 Zhen Yang,1 Cuifang Cai,1 Conglu Zhang,1 Xiaoyun Zhao,1 Minjie Wei,2 Li Yang,1 Pingtian Ding1 1School of Pharmacy, Shenyang Pharmaceutical University, 2School of Pharmacy, China Medical University, Shenyang, People’s Republic of China Abstract: G...

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Autores principales: Yu J, Zhang J, Xing H, Yang Z, Cai C, Zhang C, Zhao X, Wei M, Yang L, Ding P
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Lenguaje:EN
Publicado: Dove Medical Press 2016
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spelling oai:doaj.org-article:ecdb91689f1b4c5f9c6ebb0d356ca7002021-12-02T05:14:21ZGuanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery1178-2013https://doaj.org/article/ecdb91689f1b4c5f9c6ebb0d356ca7002016-08-01T00:00:00Zhttps://www.dovepress.com/guanidinylated-bioresponsive-polyamido-amines-designed-for-intranuclea-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jiankun Yu,1 Jinmin Zhang,1 Haonan Xing,1 Zhen Yang,1 Cuifang Cai,1 Conglu Zhang,1 Xiaoyun Zhao,1 Minjie Wei,2 Li Yang,1 Pingtian Ding1 1School of Pharmacy, Shenyang Pharmaceutical University, 2School of Pharmacy, China Medical University, Shenyang, People’s Republic of China Abstract: Guanidinylated poly(amido amine)s with multiple disulfide linkages (Gua-SS-PAAs) were designed and constructed as nonviral gene carriers. The main chains of these novel carriers were synthesized based on monomers containing guanidino groups (guanidine hydrochloride and chlorhexidine), which could avoid complicated side-chain-modification reactions while introducing the guanidino groups. The synthesized Gua-SS-PAAs polymers were characterized by 1H nuclear magnetic resonance, molecular weight, and polydispersity. Furthermore, Gua-SS-PAAs polymers were complexed with pDNA, and the properties of the complexes were determined, including entrapment efficiency, particle size, ζ-potential, atomic force microscopy images, stability, DNA complexation ability, reduction sensitivity, cytotoxicity, and transfection efficiency. The new Gua-SS-PAAs carriers exhibited higher transfection efficiency and lower cytotoxicity compared with two widely used gene delivery carriers, polyethylenimine and lipofectamine 2000. Furthermore, the relationship between the side-chain structure and morphological/biological properties was extrapolated, and the results showed that guanidine in the side chain aids in the improvement of transfection efficiency. In addition, the introduction of guanidino group might confer the new carriers with nuclear localization function compared to carriers without it. Keywords: gene carrier, transfection efficiency, cytotoxicity, nuclear localization, guanidineYu JZhang JXing HYang ZCai CZhang CZhao XWei MYang LDing PDove Medical Pressarticlegene vectortransfection efficiencyreduciblenuclear localizationguanidineMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4011-4024 (2016)
institution DOAJ
collection DOAJ
language EN
topic gene vector
transfection efficiency
reducible
nuclear localization
guanidine
Medicine (General)
R5-920
spellingShingle gene vector
transfection efficiency
reducible
nuclear localization
guanidine
Medicine (General)
R5-920
Yu J
Zhang J
Xing H
Yang Z
Cai C
Zhang C
Zhao X
Wei M
Yang L
Ding P
Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery
description Jiankun Yu,1 Jinmin Zhang,1 Haonan Xing,1 Zhen Yang,1 Cuifang Cai,1 Conglu Zhang,1 Xiaoyun Zhao,1 Minjie Wei,2 Li Yang,1 Pingtian Ding1 1School of Pharmacy, Shenyang Pharmaceutical University, 2School of Pharmacy, China Medical University, Shenyang, People’s Republic of China Abstract: Guanidinylated poly(amido amine)s with multiple disulfide linkages (Gua-SS-PAAs) were designed and constructed as nonviral gene carriers. The main chains of these novel carriers were synthesized based on monomers containing guanidino groups (guanidine hydrochloride and chlorhexidine), which could avoid complicated side-chain-modification reactions while introducing the guanidino groups. The synthesized Gua-SS-PAAs polymers were characterized by 1H nuclear magnetic resonance, molecular weight, and polydispersity. Furthermore, Gua-SS-PAAs polymers were complexed with pDNA, and the properties of the complexes were determined, including entrapment efficiency, particle size, ζ-potential, atomic force microscopy images, stability, DNA complexation ability, reduction sensitivity, cytotoxicity, and transfection efficiency. The new Gua-SS-PAAs carriers exhibited higher transfection efficiency and lower cytotoxicity compared with two widely used gene delivery carriers, polyethylenimine and lipofectamine 2000. Furthermore, the relationship between the side-chain structure and morphological/biological properties was extrapolated, and the results showed that guanidine in the side chain aids in the improvement of transfection efficiency. In addition, the introduction of guanidino group might confer the new carriers with nuclear localization function compared to carriers without it. Keywords: gene carrier, transfection efficiency, cytotoxicity, nuclear localization, guanidine
format article
author Yu J
Zhang J
Xing H
Yang Z
Cai C
Zhang C
Zhao X
Wei M
Yang L
Ding P
author_facet Yu J
Zhang J
Xing H
Yang Z
Cai C
Zhang C
Zhao X
Wei M
Yang L
Ding P
author_sort Yu J
title Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery
title_short Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery
title_full Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery
title_fullStr Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery
title_full_unstemmed Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery
title_sort guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/ecdb91689f1b4c5f9c6ebb0d356ca700
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