Stepwise targeted strategies for improving neurological function by inhibiting oxidative stress levels and inflammation following ischemic stroke
Copyright © 2024 Elsevier B.V. All rights reserved..
Ischemia-reperfusion injury is caused by excessive production of reactive oxygen species (ROS) and inflammation accompanied by ischemic injury symptoms and blood-brain barrier (BBB) dysfunction. This causes neuronal damage, for which no effective treatments or drugs exist. Herein, we provided a stepwise targeted drug delivery strategy and successfully prepared multifunctional ORDSHp@ANG nanoparticles (NPs) that consist of a stroke homing peptide (DSPE-PEG2000-SHp), BBB-targeting peptide (DSPE-PEG2000-ANG), and ROS-responsive Danshensu (salvianic acid A) chain self-assembly. ORD@SHp@ANG NPs effectively crossed the BBB by ANG peptide and selectively targeted the ischemic brain sites using stroke-homing peptide. The results showed that ORD@SHp@ANG NPs can effective at scavenging ROS, and protect SH-SY5Y cells from oxidative damage in vitro. Furthermore, ORD@SHp@ANG NPs showed excellent biocompatibility. These NPs recognized brain endothelial cells and crossed the BBB, regulated the transformation of microglia into the anti-inflammatory phenotype, and inhibited the production of inflammatory factors in a rat ischemia-reperfusion model, thereby reducing cerebral infarction, neuronal apoptosis and preserving BBB integrity. Sequencing revealed that ORD@SHp@ANG NPs promote cell proliferation, activate immune responses, suppress inflammatory responses, and ameliorate ischemic stroke. In conclusion, this study reports a simple and promising drug delivery strategy for managing ischemic stroke.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:368 |
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Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 368(2024) vom: 26. Apr., Seite 607-622 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Li, Yi [VerfasserIn] |
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Links: |
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Themen: |
Blood–brain barrier integrity |
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Anmerkungen: |
Date Completed 10.04.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.jconrel.2024.02.039 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM369133684 |
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520 | |a Ischemia-reperfusion injury is caused by excessive production of reactive oxygen species (ROS) and inflammation accompanied by ischemic injury symptoms and blood-brain barrier (BBB) dysfunction. This causes neuronal damage, for which no effective treatments or drugs exist. Herein, we provided a stepwise targeted drug delivery strategy and successfully prepared multifunctional ORDSHp@ANG nanoparticles (NPs) that consist of a stroke homing peptide (DSPE-PEG2000-SHp), BBB-targeting peptide (DSPE-PEG2000-ANG), and ROS-responsive Danshensu (salvianic acid A) chain self-assembly. ORD@SHp@ANG NPs effectively crossed the BBB by ANG peptide and selectively targeted the ischemic brain sites using stroke-homing peptide. The results showed that ORD@SHp@ANG NPs can effective at scavenging ROS, and protect SH-SY5Y cells from oxidative damage in vitro. Furthermore, ORD@SHp@ANG NPs showed excellent biocompatibility. These NPs recognized brain endothelial cells and crossed the BBB, regulated the transformation of microglia into the anti-inflammatory phenotype, and inhibited the production of inflammatory factors in a rat ischemia-reperfusion model, thereby reducing cerebral infarction, neuronal apoptosis and preserving BBB integrity. Sequencing revealed that ORD@SHp@ANG NPs promote cell proliferation, activate immune responses, suppress inflammatory responses, and ameliorate ischemic stroke. In conclusion, this study reports a simple and promising drug delivery strategy for managing ischemic stroke | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Blood–brain barrier integrity | |
650 | 4 | |a Danshensu | |
650 | 4 | |a Ischemia-reperfusion injury | |
650 | 4 | |a Neuroprotection | |
650 | 4 | |a Stepwise targeted drug delivery strategy | |
650 | 7 | |a Reactive Oxygen Species |2 NLM | |
650 | 7 | |a Peptides |2 NLM | |
700 | 1 | |a Liao, Jun |e verfasserin |4 aut | |
700 | 1 | |a Xiong, Liyan |e verfasserin |4 aut | |
700 | 1 | |a Xiao, Zhicheng |e verfasserin |4 aut | |
700 | 1 | |a Ye, Fei |e verfasserin |4 aut | |
700 | 1 | |a Wang, Yun |e verfasserin |4 aut | |
700 | 1 | |a Chen, Ting |e verfasserin |4 aut | |
700 | 1 | |a Huang, Linzhang |e verfasserin |4 aut | |
700 | 1 | |a Chen, Min |e verfasserin |4 aut | |
700 | 1 | |a Chen, Zhe-Sheng |e verfasserin |4 aut | |
700 | 1 | |a Wang, Tingfang |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Chuan |e verfasserin |4 aut | |
700 | 1 | |a Lu, Ying |e verfasserin |4 aut | |
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