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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Polymer Testing |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0142941821003378 |
| _version_ | 1818918750213111808 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T00:54:55Z |
| format | Article |
| id | doaj.art-e53d9dc9da2a45e1b10a237189b0f372 |
| institution | Directory Open Access Journal |
| issn | 0142-9418 |
| language | English |
| last_indexed | 2024-12-20T00:54:55Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Polymer Testing |
| spelling | doaj.art-e53d9dc9da2a45e1b10a237189b0f3722022-12-21T19:59:09ZengElsevierPolymer Testing0142-94182021-12-01104107392In-vivo thrombolytic efficacy of RGD modified protein-polymer conjugated urokinase nanogelsXia Liu0Ling-Li Jin1Ling-Ling Zhao2Ya-Chao Wang3Liping Zhang4Zheng-Zheng Huang5Hai-Qiang Jin6Jun-Ying Liu7Zhen-Jiang Liang8Xuan Liu9Hui Tan10Li-Jie Ren11Department of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518000, ChinaFaculty of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 315211, ChinaDepartment of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518000, China; Faculty of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 315211, China; Corresponding author. Faculty of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 315211, China.Department of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518000, ChinaDepartment of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518000, ChinaDepartment of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518000, ChinaDepartment of Neurology, Peking University First Hospital, Beijing, 100034, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Shenzhen University, Shenzhen, 518035, ChinaE.N.T. Department of Shenzhen Children's Hospital, Shenzhen, 518026, ChinaDepartment of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518000, ChinaDepartment of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518000, China; Corresponding author. Department of Neurosurgery, The First Affiliated Hospital, Shenzhen University Health Science Center, Shenzhen, 518035, China.Department of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518000, China; Corresponding author. Department of Neurology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518-000, China.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.http://www.sciencedirect.com/science/article/pii/S0142941821003378RGDpH-triggered deliveryTargeted thrombolysisStrokeBlood-brain barrier |
| spellingShingle | 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 Polymer Testing RGD pH-triggered delivery Targeted thrombolysis Stroke Blood-brain barrier |
| title | 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_short | 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 |
| topic | RGD pH-triggered delivery Targeted thrombolysis Stroke Blood-brain barrier |
| url | http://www.sciencedirect.com/science/article/pii/S0142941821003378 |
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