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

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:368

Enthalten in:

Journal of controlled release : official journal of the Controlled Release Society - 368(2024) vom: 26. Apr., Seite 607-622

Sprache:

Englisch

Beteiligte Personen:

Li, Yi [VerfasserIn]
Liao, Jun [VerfasserIn]
Xiong, Liyan [VerfasserIn]
Xiao, Zhicheng [VerfasserIn]
Ye, Fei [VerfasserIn]
Wang, Yun [VerfasserIn]
Chen, Ting [VerfasserIn]
Huang, Linzhang [VerfasserIn]
Chen, Min [VerfasserIn]
Chen, Zhe-Sheng [VerfasserIn]
Wang, Tingfang [VerfasserIn]
Zhang, Chuan [VerfasserIn]
Lu, Ying [VerfasserIn]

Links:

Volltext

Themen:

Blood–brain barrier integrity
Danshensu
Ischemia-reperfusion injury
Journal Article
Neuroprotection
Peptides
Reactive Oxygen Species
Stepwise targeted drug delivery strategy

Anmerkungen:

Date Completed 10.04.2024

Date Revised 10.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jconrel.2024.02.039

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369133684