Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

Haijun Tong,1,* Chuandong Wang,1,* Yan Huang,1,2 Qin Shi,3 Julio C Fernandes,3 Kerong Dai,1,2 Guping Tang,4 Xiaoling Zhang1,21Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (...

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Autores principales: Tong H, Wang C, Huang Y, Shi Q, Fernandes JC, Dai K, Tang G, Zhang X
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2013
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/84009402d4d64596949d9c7fae3f7a2a
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spelling oai:doaj.org-article:84009402d4d64596949d9c7fae3f7a2a2021-12-02T02:14:37ZPolyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells1176-91141178-2013https://doaj.org/article/84009402d4d64596949d9c7fae3f7a2a2013-05-01T00:00:00Zhttp://www.dovepress.com/polyethylenimine600-beta-cyclodextrin-a-promising-nanopolymer-for-nonv-a13137https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Haijun Tong,1,* Chuandong Wang,1,* Yan Huang,1,2 Qin Shi,3 Julio C Fernandes,3 Kerong Dai,1,2 Guping Tang,4 Xiaoling Zhang1,21Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Orthopaedics Research Laboratory, University of Montreal, Montreal, QC, Canada; 4Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Genetically modified mesenchymal stem cells (MSCs) have great potential in the application of regenerative medicine and molecular therapy. In the present manuscript, we introduce a nanopolymer, polyethylenimine600-β-cyclodextrin (PEI600-β-CyD), as an efficient polyplex-forming plasmid delivery agent with low toxicity and ideal transfection efficiency on primary MSCs. PEI600-β-CyD causes significantly less cytotoxicity and apoptosis on MSCs than 25 kDa high-molecular-weight PEI (PEI25kDa). PEI600-β-CyD also exhibits similar transfection efficiency as PEI25kDa on MSCs, which is higher than that of PEI600Da. Quantum dot-labeled plasmids show that PEI600-β-CyD or PEI25kDa delivers the plasmids in a more scattered manner than PEI600Da does. Further study shows that PEI600-β-CyD and PEI25kDa are more capable of delivering plasmids into the cell lysosome and nucleus than PEI600Da, which correlates well with the results of their transfection-efficiency assay. Moreover, among the three vectors, PEI600-β-CyD has the most capacity of enhancing the alkaline phosphatase activity of MSCs by transfecting bone morphogenetic protein 2, 7, or special AT-rich sequence-binding protein 2. These results clearly indicate that PEI600-β-CyD is a safe and effective candidate for the nonviral gene delivery of MSCs because of its ideal inclusion ability and proton sponge effect, and the application of this nanopolymer warrants further investigation.Keywords: polyethylenimine, cyclodextrin, gene delivery, mesenchymal stem cellsTong HWang CHuang YShi QFernandes JCDai KTang GZhang XDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1935-1946 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Tong H
Wang C
Huang Y
Shi Q
Fernandes JC
Dai K
Tang G
Zhang X
Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells
description Haijun Tong,1,* Chuandong Wang,1,* Yan Huang,1,2 Qin Shi,3 Julio C Fernandes,3 Kerong Dai,1,2 Guping Tang,4 Xiaoling Zhang1,21Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Orthopaedics Research Laboratory, University of Montreal, Montreal, QC, Canada; 4Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Genetically modified mesenchymal stem cells (MSCs) have great potential in the application of regenerative medicine and molecular therapy. In the present manuscript, we introduce a nanopolymer, polyethylenimine600-β-cyclodextrin (PEI600-β-CyD), as an efficient polyplex-forming plasmid delivery agent with low toxicity and ideal transfection efficiency on primary MSCs. PEI600-β-CyD causes significantly less cytotoxicity and apoptosis on MSCs than 25 kDa high-molecular-weight PEI (PEI25kDa). PEI600-β-CyD also exhibits similar transfection efficiency as PEI25kDa on MSCs, which is higher than that of PEI600Da. Quantum dot-labeled plasmids show that PEI600-β-CyD or PEI25kDa delivers the plasmids in a more scattered manner than PEI600Da does. Further study shows that PEI600-β-CyD and PEI25kDa are more capable of delivering plasmids into the cell lysosome and nucleus than PEI600Da, which correlates well with the results of their transfection-efficiency assay. Moreover, among the three vectors, PEI600-β-CyD has the most capacity of enhancing the alkaline phosphatase activity of MSCs by transfecting bone morphogenetic protein 2, 7, or special AT-rich sequence-binding protein 2. These results clearly indicate that PEI600-β-CyD is a safe and effective candidate for the nonviral gene delivery of MSCs because of its ideal inclusion ability and proton sponge effect, and the application of this nanopolymer warrants further investigation.Keywords: polyethylenimine, cyclodextrin, gene delivery, mesenchymal stem cells
format article
author Tong H
Wang C
Huang Y
Shi Q
Fernandes JC
Dai K
Tang G
Zhang X
author_facet Tong H
Wang C
Huang Y
Shi Q
Fernandes JC
Dai K
Tang G
Zhang X
author_sort Tong H
title Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells
title_short Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells
title_full Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells
title_fullStr Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells
title_full_unstemmed Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells
title_sort polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/84009402d4d64596949d9c7fae3f7a2a
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