Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

Wei Fan1,2,*, Xin Wu1,*, Baoyue Ding3,*, Jing Gao4, Zhen Cai1, Wei Zhang1, Dongfeng Yin1, Xiang Wang1, Quangang Zhu1, Jiyong Liu1, Xueying Ding4, Shen Gao1 1Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 2Department of Pharmaceutics, The 425th Hospital...

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Autores principales: Ding X, Liu J, Zhu Q, Wang X, Yin D, Zhang W, Cai Z, Gao J, Ding B, Wu X, Fan W, Gao S
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Publicado: Dove Medical Press 2012
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spelling oai:doaj.org-article:22d073a233d24d769913dff49ad1bacb2021-12-02T06:34:19ZDegradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution1176-91141178-2013https://doaj.org/article/22d073a233d24d769913dff49ad1bacb2012-02-01T00:00:00Zhttp://www.dovepress.com/degradable-gene-delivery-systems-based-on-pluronics-modified-low-molec-a9353https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Wei Fan1,2,*, Xin Wu1,*, Baoyue Ding3,*, Jing Gao4, Zhen Cai1, Wei Zhang1, Dongfeng Yin1, Xiang Wang1, Quangang Zhu1, Jiyong Liu1, Xueying Ding4, Shen Gao1 1Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 2Department of Pharmaceutics, The 425th Hospital of PLA, Sanya, 3Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, 4Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China*These authors contributed equally to this workBackground: Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers' structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake.Methods: This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic® consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers.Results: Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophilic-lipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus.Conclusion: This Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future.Keywords: Pluronics, gene transfer, nonviral vectors, transfection efficiency, cellular uptakeDing XLiu JZhu QWang XYin DZhang WCai ZGao JDing BWu XFan WGao SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 1127-1138 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Ding X
Liu J
Zhu Q
Wang X
Yin D
Zhang W
Cai Z
Gao J
Ding B
Wu X
Fan W
Gao S
Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution
description Wei Fan1,2,*, Xin Wu1,*, Baoyue Ding3,*, Jing Gao4, Zhen Cai1, Wei Zhang1, Dongfeng Yin1, Xiang Wang1, Quangang Zhu1, Jiyong Liu1, Xueying Ding4, Shen Gao1 1Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 2Department of Pharmaceutics, The 425th Hospital of PLA, Sanya, 3Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, 4Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China*These authors contributed equally to this workBackground: Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers' structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake.Methods: This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic® consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers.Results: Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophilic-lipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus.Conclusion: This Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future.Keywords: Pluronics, gene transfer, nonviral vectors, transfection efficiency, cellular uptake
format article
author Ding X
Liu J
Zhu Q
Wang X
Yin D
Zhang W
Cai Z
Gao J
Ding B
Wu X
Fan W
Gao S
author_facet Ding X
Liu J
Zhu Q
Wang X
Yin D
Zhang W
Cai Z
Gao J
Ding B
Wu X
Fan W
Gao S
author_sort Ding X
title Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution
title_short Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution
title_full Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution
title_fullStr Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution
title_full_unstemmed Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution
title_sort degradable gene delivery systems based on pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/22d073a233d24d769913dff49ad1bacb
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