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Transferrin-Enabled Blood–Brain Barrier Crossing Manganese-Based Nanozyme for Rebalancing the Reactive Oxygen Species Level in Ischemic Stroke

(1) Background: Acute ischemic stroke (IS) is one of the main causes of human disability and death. Therefore, multifunctional nanosystems that effectively cross the blood–brain barrier (BBB) and efficiently eliminate reactive oxygen species (ROS) are urgently needed for comprehensive neuroprotectiv...

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Autores principales: Zhao, Qianqian, Du, Wenxian, Zhou, Lingling, Wu, Jianrong, Zhang, Xiaoxing, Wei, Xiaoer, Wang, Sijia, Huang, Yu, Li, Yuehua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231148/
https://www.ncbi.nlm.nih.gov/pubmed/35745695
http://dx.doi.org/10.3390/pharmaceutics14061122
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author Zhao, Qianqian
Du, Wenxian
Zhou, Lingling
Wu, Jianrong
Zhang, Xiaoxing
Wei, Xiaoer
Wang, Sijia
Huang, Yu
Li, Yuehua
author_facet Zhao, Qianqian
Du, Wenxian
Zhou, Lingling
Wu, Jianrong
Zhang, Xiaoxing
Wei, Xiaoer
Wang, Sijia
Huang, Yu
Li, Yuehua
author_sort Zhao, Qianqian
collection PubMed
description (1) Background: Acute ischemic stroke (IS) is one of the main causes of human disability and death. Therefore, multifunctional nanosystems that effectively cross the blood–brain barrier (BBB) and efficiently eliminate reactive oxygen species (ROS) are urgently needed for comprehensive neuroprotective effects. (2) Methods: We designed a targeted transferrin (Tf)-based manganese dioxide nanozyme (MnO(2)@Tf, MT) using a mild biomimetic mineralization method for rebalancing ROS levels. Furthermore, MT can be efficiently loaded with edaravone (Eda), a clinical neuroprotective agent, to obtain the Eda-MnO(2)@Tf (EMT) nanozyme. (3) Results: The EMT nanozyme not only accumulates in a lesion area and crosses the BBB but also possesses satisfactory biocompatibility and biosafety based on the functional inheritance of Tf. Meanwhile, EMT has intrinsic hydroxyl radical-scavenging ability and superoxide-dismutase-like and catalase-like nanozyme abilities, allowing it to ameliorate ROS-mediated damage and decrease inflammatory factor levels in vivo. Moreover, the released Mn(2+) ions in the weak acid environment of the lesion area can be used for magnetic resonance imaging (MRI) to monitor the treatment process. (4) Conclusions: Our study not only paves a way to engineer alternative targeted ROS scavengers for intensive reperfusion-induced injury in ischemic stroke but also provides new insights into the construction of bioinspired Mn-based nanozymes.
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spelling pubmed-92311482022-06-25 Transferrin-Enabled Blood–Brain Barrier Crossing Manganese-Based Nanozyme for Rebalancing the Reactive Oxygen Species Level in Ischemic Stroke Zhao, Qianqian Du, Wenxian Zhou, Lingling Wu, Jianrong Zhang, Xiaoxing Wei, Xiaoer Wang, Sijia Huang, Yu Li, Yuehua Pharmaceutics Article (1) Background: Acute ischemic stroke (IS) is one of the main causes of human disability and death. Therefore, multifunctional nanosystems that effectively cross the blood–brain barrier (BBB) and efficiently eliminate reactive oxygen species (ROS) are urgently needed for comprehensive neuroprotective effects. (2) Methods: We designed a targeted transferrin (Tf)-based manganese dioxide nanozyme (MnO(2)@Tf, MT) using a mild biomimetic mineralization method for rebalancing ROS levels. Furthermore, MT can be efficiently loaded with edaravone (Eda), a clinical neuroprotective agent, to obtain the Eda-MnO(2)@Tf (EMT) nanozyme. (3) Results: The EMT nanozyme not only accumulates in a lesion area and crosses the BBB but also possesses satisfactory biocompatibility and biosafety based on the functional inheritance of Tf. Meanwhile, EMT has intrinsic hydroxyl radical-scavenging ability and superoxide-dismutase-like and catalase-like nanozyme abilities, allowing it to ameliorate ROS-mediated damage and decrease inflammatory factor levels in vivo. Moreover, the released Mn(2+) ions in the weak acid environment of the lesion area can be used for magnetic resonance imaging (MRI) to monitor the treatment process. (4) Conclusions: Our study not only paves a way to engineer alternative targeted ROS scavengers for intensive reperfusion-induced injury in ischemic stroke but also provides new insights into the construction of bioinspired Mn-based nanozymes. MDPI 2022-05-25 /pmc/articles/PMC9231148/ /pubmed/35745695 http://dx.doi.org/10.3390/pharmaceutics14061122 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Qianqian
Du, Wenxian
Zhou, Lingling
Wu, Jianrong
Zhang, Xiaoxing
Wei, Xiaoer
Wang, Sijia
Huang, Yu
Li, Yuehua
Transferrin-Enabled Blood–Brain Barrier Crossing Manganese-Based Nanozyme for Rebalancing the Reactive Oxygen Species Level in Ischemic Stroke
title Transferrin-Enabled Blood–Brain Barrier Crossing Manganese-Based Nanozyme for Rebalancing the Reactive Oxygen Species Level in Ischemic Stroke
title_full Transferrin-Enabled Blood–Brain Barrier Crossing Manganese-Based Nanozyme for Rebalancing the Reactive Oxygen Species Level in Ischemic Stroke
title_fullStr Transferrin-Enabled Blood–Brain Barrier Crossing Manganese-Based Nanozyme for Rebalancing the Reactive Oxygen Species Level in Ischemic Stroke
title_full_unstemmed Transferrin-Enabled Blood–Brain Barrier Crossing Manganese-Based Nanozyme for Rebalancing the Reactive Oxygen Species Level in Ischemic Stroke
title_short Transferrin-Enabled Blood–Brain Barrier Crossing Manganese-Based Nanozyme for Rebalancing the Reactive Oxygen Species Level in Ischemic Stroke
title_sort transferrin-enabled blood–brain barrier crossing manganese-based nanozyme for rebalancing the reactive oxygen species level in ischemic stroke
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231148/
https://www.ncbi.nlm.nih.gov/pubmed/35745695
http://dx.doi.org/10.3390/pharmaceutics14061122
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