A polymerized probucol nanoformulation with neutrophil extracellular vesicle camouflage for cerebral ischemia-reperfusion injury therapy

Summary: This study leverages the unique advantages of polyprodrug systems and biomimetic technology to develop a novel biomimetic nanoformulation, in which neutrophil extracellular vesicles (NEVs) are coated onto reactive oxygen species (ROS)-sensitive probucol-based polyprodrug nanoparticles (NPPB...

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Main Authors: Mengjie Jia, Wenjun Miao, Yiliang Li, Yajie Guo, Jieying Zeng, Yan Gao, Xinting Li, Yufan Wang, Zhenghuan Zhao, Zichen Xu, Nancy Wang, Fang Yang, Jing Zhao, Yi Wang, Guixue Wang
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:The Innovation
Online Access:http://www.sciencedirect.com/science/article/pii/S2666675824001991
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Summary:Summary: This study leverages the unique advantages of polyprodrug systems and biomimetic technology to develop a novel biomimetic nanoformulation, in which neutrophil extracellular vesicles (NEVs) are coated onto reactive oxygen species (ROS)-sensitive probucol-based polyprodrug nanoparticles (NPPBNPs). This NEV-camouflaged biomimetic nanoformulation holds significant potential for the effective treatment of cerebral ischemia-reperfusion injury (CIRI), offering multifaceted therapeutic effects, such as ROS elimination, inhibition of oxidative stress-induced neuronal apoptosis, attenuation of glial hyperactivation, and suppression of pro-inflammatory mediator secretion. In a murine CIRI model, NPPBNPs markedly enhanced neuronal viability, ameliorated the ischemic penumbra, restored behavioral functions, and exhibited an acceptable safety profile. The therapeutic mechanism of NPPBNPs involves NEV-mediated camouflage, which enables selective targeting of the pathological endothelium, thereby reducing peripheral neutrophil recruitment and facilitating blood-brain barrier (BBB) transport. Upon internalization by neurons, astrocytes, and microglia within ischemic regions, NPPBNPs respond to elevated intracellular ROS levels by releasing probucol in a controlled manner, which synergistically mitigates oxidative stress and inflammatory responses in CIRI-affected areas. Collectively, this multifunctional biomimetic nanoformulation represents a promising and practical strategy for the safe and effective treatment of CIRI.
ISSN:2666-6758