In-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogels

It has been shown that an arginine-glycine-aspartic acid (RGD) modified pH-triggered delivery system for the urokinase-type plasminogen activator (uPA) is resistant to enzymatic degradation and improves thrombolytic ability in vitro. Herein, we aimed to compare the thrombolytic efficacies of uPA-oxi...

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Autores principales:	Xia Liu, Ling-Li Jin, Ling-Ling Zhao, Ya-Chao Wang, Liping Zhang, Zheng-Zheng Huang, Hai-Qiang Jin, Jun-Ying Liu, Zhen-Jiang Liang, Xuan Liu, Hui Tan, Li-Jie Ren
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	RGD pH-triggered delivery Targeted thrombolysis Stroke Blood-brain barrier Polymers and polymer manufacture TP1080-1185
Acceso en línea:	https://doaj.org/article/e53d9dc9da2a45e1b10a237189b0f372
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spelling	oai:doaj.org-article:e53d9dc9da2a45e1b10a237189b0f3722021-11-14T04:27:59ZIn-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogels0142-941810.1016/j.polymertesting.2021.107392https://doaj.org/article/e53d9dc9da2a45e1b10a237189b0f3722021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0142941821003378https://doaj.org/toc/0142-9418It has been shown that an arginine-glycine-aspartic acid (RGD) modified pH-triggered delivery system for the urokinase-type plasminogen activator (uPA) is resistant to enzymatic degradation and improves thrombolytic ability in vitro. Herein, we aimed to compare the thrombolytic efficacies of uPA-oxidized dextran (Oxd)-RGD and uPA using a rat model of middle cerebral ischemia occlusion (MCAO) in vivo. We found that the uPA-Oxd conjugates delayed the release of active uPA after MCAO. Thus, the rats treated with uPA-Oxd-RGD showed significantly decreased neurological deficits and infarct volume compared with those of the rats treated with uPA alone after MCAO. Furthermore, the administration of uPA-Oxd-RGD attenuated blood–brain barrier disruption and downregulated matrix metalloproteinase expression while upregulating the expression of tight junction proteins. In addition, uPA-Oxd-RGD inhibited apoptosis by suppressing pro-apoptotic caspase expression. These results suggest that the administration of uPA-Oxd-RGD is a more effective intervention in an MCAO model than uPA alone and that the pH changes in the brain tissue after an ischemic stroke may be a novel thrombolytic target.Xia LiuLing-Li JinLing-Ling ZhaoYa-Chao WangLiping ZhangZheng-Zheng HuangHai-Qiang JinJun-Ying LiuZhen-Jiang LiangXuan LiuHui TanLi-Jie RenElsevierarticleRGDpH-triggered deliveryTargeted thrombolysisStrokeBlood-brain barrierPolymers and polymer manufactureTP1080-1185ENPolymer Testing, Vol 104, Iss , Pp 107392- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RGD pH-triggered delivery Targeted thrombolysis Stroke Blood-brain barrier Polymers and polymer manufacture TP1080-1185
spellingShingle	RGD pH-triggered delivery Targeted thrombolysis Stroke Blood-brain barrier Polymers and polymer manufacture TP1080-1185 Xia Liu Ling-Li Jin Ling-Ling Zhao Ya-Chao Wang Liping Zhang Zheng-Zheng Huang Hai-Qiang Jin Jun-Ying Liu Zhen-Jiang Liang Xuan Liu Hui Tan Li-Jie Ren In-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogels
description	It has been shown that an arginine-glycine-aspartic acid (RGD) modified pH-triggered delivery system for the urokinase-type plasminogen activator (uPA) is resistant to enzymatic degradation and improves thrombolytic ability in vitro. Herein, we aimed to compare the thrombolytic efficacies of uPA-oxidized dextran (Oxd)-RGD and uPA using a rat model of middle cerebral ischemia occlusion (MCAO) in vivo. We found that the uPA-Oxd conjugates delayed the release of active uPA after MCAO. Thus, the rats treated with uPA-Oxd-RGD showed significantly decreased neurological deficits and infarct volume compared with those of the rats treated with uPA alone after MCAO. Furthermore, the administration of uPA-Oxd-RGD attenuated blood–brain barrier disruption and downregulated matrix metalloproteinase expression while upregulating the expression of tight junction proteins. In addition, uPA-Oxd-RGD inhibited apoptosis by suppressing pro-apoptotic caspase expression. These results suggest that the administration of uPA-Oxd-RGD is a more effective intervention in an MCAO model than uPA alone and that the pH changes in the brain tissue after an ischemic stroke may be a novel thrombolytic target.
format	article
author	Xia Liu Ling-Li Jin Ling-Ling Zhao Ya-Chao Wang Liping Zhang Zheng-Zheng Huang Hai-Qiang Jin Jun-Ying Liu Zhen-Jiang Liang Xuan Liu Hui Tan Li-Jie Ren
author_facet	Xia Liu Ling-Li Jin Ling-Ling Zhao Ya-Chao Wang Liping Zhang Zheng-Zheng Huang Hai-Qiang Jin Jun-Ying Liu Zhen-Jiang Liang Xuan Liu Hui Tan Li-Jie Ren
author_sort	Xia Liu
title	In-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogels
title_short	In-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogels
title_full	In-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogels
title_fullStr	In-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogels
title_full_unstemmed	In-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogels
title_sort	in-vivo thrombolytic efficacy of rgd modified protein-polymer conjugated urokinase nanogels
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/e53d9dc9da2a45e1b10a237189b0f372
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In-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogels

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