Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells

Guo-dong Wang, Yu-zhen Tan, Hai-jie Wang, Pei Zhou Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China Abstract: Polyethyleneimine (PEI)–alginate (Alg) nanoparticle (NP) is a safe and effective vector for delivery of siRNA or DNA....

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Autores principales: Wang GD, Tan YZ, Wang HJ, Zhou P
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Lenguaje:EN
Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:a127729cfaf74f67af17acbe5f0de6c42021-12-02T05:08:58ZAutophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells1178-2013https://doaj.org/article/a127729cfaf74f67af17acbe5f0de6c42017-09-01T00:00:00Zhttps://www.dovepress.com/autophagy-promotes-degradation-of-polyethyleneimine-alginate-nanoparti-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Guo-dong Wang, Yu-zhen Tan, Hai-jie Wang, Pei Zhou Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China Abstract: Polyethyleneimine (PEI)–alginate (Alg) nanoparticle (NP) is a safe and effective vector for delivery of siRNA or DNA. Recent studies suggest that autophagy is related to cytotoxicity of PEI NPs. However, contribution of autophagy to degradation of PEI–Alg NPs remains unknown. CD34+VEGFR-3+ endothelial progenitor cells isolated from rat bone marrow were treated with 25 kDa branched PEI modified by Alg. After treatment with the NPs, morphological changes and distribution of the NPs in the cells were examined with scanning and transmission electron microscopies. Cytotoxicity of the NPs was analyzed by reactive oxygen species (ROS) production, lactate dehydrogenase leakage and induction of apoptosis. The level of autophagy was assessed with expression of Beclin-1 and LC3 and formation of autophagic structures and amphisomes. Colocalization of LC3-positive puncta and the NPs was determined by LC3–GFP tracing. Cytotoxicity of PEI NPs was reduced greatly after modification with Alg. PEI–Alg NPs were distributed in mitochondria, rough endoplasmic reticula and nuclei as well as cytoplasm. After phagocytosis of the NPs, expression of Beclin-1 mRNA and LC3 protein was upregulated, and the number of LC3-positive puncta, autophagic structures and amphisomes increased significantly. The number of lysosomes also increased obviously. There were LC3-positive puncta in nuclei, and some puncta were colocalized with the NPs. These results demonstrate that the activated autophagy promotes degradation of PEI–Alg NPs via multiple pathways. Keywords: polyethyleneimine, alginate, nanoparticles, endothelial progenitor cells, autophagyWang GDTan YZWang HJZhou PDove Medical Pressarticlepolyethyleneiminealginatenanoparticlesendothelial progenitor cellsautophagyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6661-6675 (2017)
institution DOAJ
collection DOAJ
language EN
topic polyethyleneimine
alginate
nanoparticles
endothelial progenitor cells
autophagy
Medicine (General)
R5-920
spellingShingle polyethyleneimine
alginate
nanoparticles
endothelial progenitor cells
autophagy
Medicine (General)
R5-920
Wang GD
Tan YZ
Wang HJ
Zhou P
Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells
description Guo-dong Wang, Yu-zhen Tan, Hai-jie Wang, Pei Zhou Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China Abstract: Polyethyleneimine (PEI)–alginate (Alg) nanoparticle (NP) is a safe and effective vector for delivery of siRNA or DNA. Recent studies suggest that autophagy is related to cytotoxicity of PEI NPs. However, contribution of autophagy to degradation of PEI–Alg NPs remains unknown. CD34+VEGFR-3+ endothelial progenitor cells isolated from rat bone marrow were treated with 25 kDa branched PEI modified by Alg. After treatment with the NPs, morphological changes and distribution of the NPs in the cells were examined with scanning and transmission electron microscopies. Cytotoxicity of the NPs was analyzed by reactive oxygen species (ROS) production, lactate dehydrogenase leakage and induction of apoptosis. The level of autophagy was assessed with expression of Beclin-1 and LC3 and formation of autophagic structures and amphisomes. Colocalization of LC3-positive puncta and the NPs was determined by LC3–GFP tracing. Cytotoxicity of PEI NPs was reduced greatly after modification with Alg. PEI–Alg NPs were distributed in mitochondria, rough endoplasmic reticula and nuclei as well as cytoplasm. After phagocytosis of the NPs, expression of Beclin-1 mRNA and LC3 protein was upregulated, and the number of LC3-positive puncta, autophagic structures and amphisomes increased significantly. The number of lysosomes also increased obviously. There were LC3-positive puncta in nuclei, and some puncta were colocalized with the NPs. These results demonstrate that the activated autophagy promotes degradation of PEI–Alg NPs via multiple pathways. Keywords: polyethyleneimine, alginate, nanoparticles, endothelial progenitor cells, autophagy
format article
author Wang GD
Tan YZ
Wang HJ
Zhou P
author_facet Wang GD
Tan YZ
Wang HJ
Zhou P
author_sort Wang GD
title Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells
title_short Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells
title_full Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells
title_fullStr Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells
title_full_unstemmed Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells
title_sort autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/a127729cfaf74f67af17acbe5f0de6c4
work_keys_str_mv AT wanggd autophagypromotesdegradationofpolyethyleneiminendashalginatenanoparticlesinendothelialprogenitorcells
AT tanyz autophagypromotesdegradationofpolyethyleneiminendashalginatenanoparticlesinendothelialprogenitorcells
AT wanghj autophagypromotesdegradationofpolyethyleneiminendashalginatenanoparticlesinendothelialprogenitorcells
AT zhoup autophagypromotesdegradationofpolyethyleneiminendashalginatenanoparticlesinendothelialprogenitorcells
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