Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine

Lu Hou,1,2 Zheyu Song,3 Zhonghang Xu,3 Yuanyu Wu,3 Wei Shi1,2 1College of Life Science, Jilin University, Changchun, Jilin 130012, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130012, People&rsq...

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Autores principales:	Hou L, Song Z, Xu Z, Wu Y, Shi W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	targeted delivery folate leucine-bearing pei siplk1 gene therapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/df74bcbd00164dacb83fd6857264bd0e
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spelling	oai:doaj.org-article:df74bcbd00164dacb83fd6857264bd0e2021-12-02T09:37:08ZFolate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine1178-2013https://doaj.org/article/df74bcbd00164dacb83fd6857264bd0e2020-03-01T00:00:00Zhttps://www.dovepress.com/folate-mediated-targeted-delivery-of-siplk1-by-leucine-bearing-polyeth-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lu Hou,1,2 Zheyu Song,3 Zhonghang Xu,3 Yuanyu Wu,3 Wei Shi1,2 1College of Life Science, Jilin University, Changchun, Jilin 130012, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130012, People’s Republic of China; 3Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, Changchun 130033, People’s Republic of ChinaCorrespondence: Wei ShiKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, People’s Republic of ChinaTel +86-431-85155216Fax +86-431-85155200Email shiw@jlu.edu.cnBackground: siRNA-mediated polo-like kinase 1 (PLK1) silencing has been proposed as a promising therapeutic method for multiple cancers. However, the clinic application of this method is still hindered by the low specific delivery of siPLK1 to desired tumor lesions. Herein, folate (FA)-modified and leucine-bearing polyethylenimine was successfully synthesized and showed excellent targeted silencing to folate receptor overexpressed cells.Materials and Methods: The condensation of siPLK1 by FA-N-Ac-L-Leu-PEI (NPF) was detected by the gel retardation assay. The targeted and silencing efficiency was evaluated by flow cytometry and confocal laser scanning microscope. The PLK1 expressions at gene or protein levels were detected by quantitative real-time PCR and Western blotting assay. Further impacts of the PLK1 silencing on cell viability, cell cycle, migration, and invasion were studied by MTT, colony formation, wound healing and transwell assays.Results: The NPF and siPLK1 could efficiently assemble to stable nanoparticles at a weight ratio of 3.0 and showed excellent condensation and protection effect. Owing to the FA-mediated targeted delivery, the uptake and silencing efficiency of NPF/siPLK1 to SGC-7901 cells was higher than that without FA modification. Moreover, NPF-mediated PLK1 silencing showed significant antitumor activity in vitro. The anti-proliferation effect of PLK1 silencing was induced via the mitochondrial-dependent apoptosis pathway with the cell cycle arrest of 45% at G2 phase and the apoptotic ratio of 28.3%.Conclusion: FA-N-Ac-L-Leu-PEI (NPF) could generate targeted delivery siPLK1 to FA receptor overexpressed cells and dramatically downregulate the expression of PLK1 expression.Keywords: targeted delivery, folate, leucine-bearing PEI, siPLK1, gene therapyHou LSong ZXu ZWu YShi WDove Medical Pressarticletargeted deliveryfolateleucine-bearing peisiplk1gene therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1397-1408 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	targeted delivery folate leucine-bearing pei siplk1 gene therapy Medicine (General) R5-920
spellingShingle	targeted delivery folate leucine-bearing pei siplk1 gene therapy Medicine (General) R5-920 Hou L Song Z Xu Z Wu Y Shi W Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine
description	Lu Hou,1,2 Zheyu Song,3 Zhonghang Xu,3 Yuanyu Wu,3 Wei Shi1,2 1College of Life Science, Jilin University, Changchun, Jilin 130012, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130012, People’s Republic of China; 3Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, Changchun 130033, People’s Republic of ChinaCorrespondence: Wei ShiKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, People’s Republic of ChinaTel +86-431-85155216Fax +86-431-85155200Email shiw@jlu.edu.cnBackground: siRNA-mediated polo-like kinase 1 (PLK1) silencing has been proposed as a promising therapeutic method for multiple cancers. However, the clinic application of this method is still hindered by the low specific delivery of siPLK1 to desired tumor lesions. Herein, folate (FA)-modified and leucine-bearing polyethylenimine was successfully synthesized and showed excellent targeted silencing to folate receptor overexpressed cells.Materials and Methods: The condensation of siPLK1 by FA-N-Ac-L-Leu-PEI (NPF) was detected by the gel retardation assay. The targeted and silencing efficiency was evaluated by flow cytometry and confocal laser scanning microscope. The PLK1 expressions at gene or protein levels were detected by quantitative real-time PCR and Western blotting assay. Further impacts of the PLK1 silencing on cell viability, cell cycle, migration, and invasion were studied by MTT, colony formation, wound healing and transwell assays.Results: The NPF and siPLK1 could efficiently assemble to stable nanoparticles at a weight ratio of 3.0 and showed excellent condensation and protection effect. Owing to the FA-mediated targeted delivery, the uptake and silencing efficiency of NPF/siPLK1 to SGC-7901 cells was higher than that without FA modification. Moreover, NPF-mediated PLK1 silencing showed significant antitumor activity in vitro. The anti-proliferation effect of PLK1 silencing was induced via the mitochondrial-dependent apoptosis pathway with the cell cycle arrest of 45% at G2 phase and the apoptotic ratio of 28.3%.Conclusion: FA-N-Ac-L-Leu-PEI (NPF) could generate targeted delivery siPLK1 to FA receptor overexpressed cells and dramatically downregulate the expression of PLK1 expression.Keywords: targeted delivery, folate, leucine-bearing PEI, siPLK1, gene therapy
format	article
author	Hou L Song Z Xu Z Wu Y Shi W
author_facet	Hou L Song Z Xu Z Wu Y Shi W
author_sort	Hou L
title	Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine
title_short	Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine
title_full	Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine
title_fullStr	Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine
title_full_unstemmed	Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine
title_sort	folate-mediated targeted delivery of siplk1 by leucine-bearing polyethylenimine
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/df74bcbd00164dacb83fd6857264bd0e
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Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine

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