Neutrophil Membrane-Camouflaged Polyprodrug Nanomedicine for Inflammation Suppression in Ischemic Stroke Therapy

Neutrophil Membrane-Camouflaged Polyprodrug Nanomedicine for Inflammation Suppression in Ischemic Stroke Therapy

© 2024 Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 21 vom: 03. Mai, Seite e2311803
1. Verfasser: Zhao, Ya (VerfasserIn)
Weitere Verfasser: Li, Qian, Niu, Jingyan, Guo, Erliang, Zhao, Chenchen, Zhang, Jian, Liu, Xue, Wang, Lihua, Rao, Lang, Chen, Xiaoyuan, Yang, Kuikun
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article anti‐inflammation blood–brain barrier ischemic stroke nanomedicine polyprodrug scRNA‐seq Fingolimod Hydrochloride G926EC510T Prodrugs mehr... NLR Family, Pyrin Domain-Containing 3 Protein Anti-Inflammatory Agents Reactive Oxygen Species Neuroprotective Agents
Beschreibung
Zusammenfassung:© 2024 Wiley‐VCH GmbH.
Neuroinflammation has emerged as a major concern in ischemic stroke therapy because it exacebates neurological dysfunction and suppresses neurological recovery after ischemia/reperfusion. Fingolimod hydrochloride (FTY720) is an FDA-approved anti-inflammatory drug which exhibits potential neuroprotective effects in ischemic brain parenchyma. However, delivering a sufficient amount of FTY720 through the blood-brain barrier into brain lesions without inducing severe cardiovascular side effects remains challenging. Here, a neutrophil membrane-camouflaged polyprodrug nanomedicine that can migrate into ischemic brain tissues and in situ release FTY720 in response to elevated levels of reactive oxygen species. This nanomedicine delivers 15.2-fold more FTY720 into the ischemic brain and significantly reduces the risk of cardiotoxicity and infection compared with intravenously administered free drug. In addition, single-cell RNA-sequencing analysis identifies that the nanomedicine attenuates poststroke inflammation by reprogramming microglia toward anti-inflammatory phenotypes, which is realized via modulating Cebpb-regulated activation of NLRP3 inflammasomes and secretion of CXCL2 chemokine. This study offers new insights into the design and fabrication of polyprodrug nanomedicines for effective suppression of inflammation in ischemic stroke therapy
Beschreibung:Date Completed 24.05.2024
Date Revised 24.05.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202311803