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Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress

Oxidation resistance 1 (OXR1) is regarded as a critical regulator of cellular homeostasis in response to oxidative stress. However, the role of OXR1 in the neuronal response to spinal cord injury (SCI) remains undefined. On the other hand, gene therapy for SCI has shown limited success to date due i...

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Autores principales: Zhang, Jing, Li, Yao, Xiong, Jun, Xu, Helin, Xiang, Guanghen, Fan, Mingqiao, Zhou, Kailiang, Lin, Yutian, Chen, Xiangxiang, Xie, Lin, Zhang, Hongyu, Wang, Jian, Xiao, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970014/
https://www.ncbi.nlm.nih.gov/pubmed/33778197
http://dx.doi.org/10.1016/j.bioactmat.2021.03.001
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author Zhang, Jing
Li, Yao
Xiong, Jun
Xu, Helin
Xiang, Guanghen
Fan, Mingqiao
Zhou, Kailiang
Lin, Yutian
Chen, Xiangxiang
Xie, Lin
Zhang, Hongyu
Wang, Jian
Xiao, Jian
author_facet Zhang, Jing
Li, Yao
Xiong, Jun
Xu, Helin
Xiang, Guanghen
Fan, Mingqiao
Zhou, Kailiang
Lin, Yutian
Chen, Xiangxiang
Xie, Lin
Zhang, Hongyu
Wang, Jian
Xiao, Jian
author_sort Zhang, Jing
collection PubMed
description Oxidation resistance 1 (OXR1) is regarded as a critical regulator of cellular homeostasis in response to oxidative stress. However, the role of OXR1 in the neuronal response to spinal cord injury (SCI) remains undefined. On the other hand, gene therapy for SCI has shown limited success to date due in part to the poor utility of conventional gene vectors. In this study, we evaluated the function of OXR1 in SCI and developed an available carrier for delivering the OXR1 plasmid (pOXR1). We found that OXR1 expression is remarkably increased after SCI and that this regulation is protective after SCI. Meanwhile, we assembled cationic nanoparticles with vitamin E succinate-grafted ε-polylysine (VES-g-PLL) (Nps). The pOXR1 was precompressed with Nps and then encapsulated into cationic liposomes. The particle size of pOXR1 was compressed to 58 nm, which suggests that pOXR1 can be encapsulated inside liposomes with high encapsulation efficiency and stability to enhance the transfection efficiency. The agarose gel results indicated that Nps-pOXR1-Lip eliminated the degradation of DNA by DNase I and maintained its activity, and the cytotoxicity results indicated that pOXR1 was successfully transported into cells and exhibited lower cytotoxicity. Finally, Nps-pOXR1-Lip promoted functional recovery by alleviating neuronal apoptosis, attenuating oxidative stress and inhibiting inflammation. Therefore, our study provides considerable evidence that OXR1 is a beneficial factor in resistance to SCI and that Nps-Lip-pOXR1 exerts therapeutic effects in acute traumatic SCI.
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spelling pubmed-79700142021-03-25 Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress Zhang, Jing Li, Yao Xiong, Jun Xu, Helin Xiang, Guanghen Fan, Mingqiao Zhou, Kailiang Lin, Yutian Chen, Xiangxiang Xie, Lin Zhang, Hongyu Wang, Jian Xiao, Jian Bioact Mater Article Oxidation resistance 1 (OXR1) is regarded as a critical regulator of cellular homeostasis in response to oxidative stress. However, the role of OXR1 in the neuronal response to spinal cord injury (SCI) remains undefined. On the other hand, gene therapy for SCI has shown limited success to date due in part to the poor utility of conventional gene vectors. In this study, we evaluated the function of OXR1 in SCI and developed an available carrier for delivering the OXR1 plasmid (pOXR1). We found that OXR1 expression is remarkably increased after SCI and that this regulation is protective after SCI. Meanwhile, we assembled cationic nanoparticles with vitamin E succinate-grafted ε-polylysine (VES-g-PLL) (Nps). The pOXR1 was precompressed with Nps and then encapsulated into cationic liposomes. The particle size of pOXR1 was compressed to 58 nm, which suggests that pOXR1 can be encapsulated inside liposomes with high encapsulation efficiency and stability to enhance the transfection efficiency. The agarose gel results indicated that Nps-pOXR1-Lip eliminated the degradation of DNA by DNase I and maintained its activity, and the cytotoxicity results indicated that pOXR1 was successfully transported into cells and exhibited lower cytotoxicity. Finally, Nps-pOXR1-Lip promoted functional recovery by alleviating neuronal apoptosis, attenuating oxidative stress and inhibiting inflammation. Therefore, our study provides considerable evidence that OXR1 is a beneficial factor in resistance to SCI and that Nps-Lip-pOXR1 exerts therapeutic effects in acute traumatic SCI. KeAi Publishing 2021-03-10 /pmc/articles/PMC7970014/ /pubmed/33778197 http://dx.doi.org/10.1016/j.bioactmat.2021.03.001 Text en © 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zhang, Jing
Li, Yao
Xiong, Jun
Xu, Helin
Xiang, Guanghen
Fan, Mingqiao
Zhou, Kailiang
Lin, Yutian
Chen, Xiangxiang
Xie, Lin
Zhang, Hongyu
Wang, Jian
Xiao, Jian
Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress
title Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress
title_full Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress
title_fullStr Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress
title_full_unstemmed Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress
title_short Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress
title_sort delivery of poxr1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970014/
https://www.ncbi.nlm.nih.gov/pubmed/33778197
http://dx.doi.org/10.1016/j.bioactmat.2021.03.001
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