Intranasal blood-brain barrier bypass enables sequential mitochondria-targeted bioengineered nanolamellar system for ischemic stroke therapy

Yin, Yue; Li, Zixuan; Shu, Weijie; Liu, H. Y.; Wang, Zihan; Fu, Cong; Zhu, Yuanbo; Li, X.; Zhang, Yi; Lv, Bei; Wang, Zixuan; Zhao, Qiaoqiao; Liu, Dan; Tang, Lu; Wang, Wei

doi:10.1038/s41467-025-68024-5

articleNature CommunicationsJan 17, 2026GOLD OA

Intranasal blood-brain barrier bypass enables sequential mitochondria-targeted bioengineered nanolamellar system for ischemic stroke therapy

YYYue Yin ZLZixuan Li WSWeijie Shu HYH. Y. Liu ZWZihan Wang

China Pharmaceutical University · German Center for Neurodegenerative Diseases · +1 more institution

PubMed

Indexed incrossrefdoajpubmed

Abstract

Mitochondrial damage constitutes the central pathological mechanism of cerebral ischemia-reperfusion (I/R) injury. Targeted delivery of antioxidants to mitochondria and the phenotype polarization of glial cells holds great promise for effective treatment. However, the blood-brain barrier (BBB) remains a major obstacle, causing insufficient drug accumulation in neuronal mitochondria. Here, we develop a bioengineered nanolamellar system (MM@BPPF) by coating microglia-mitochondria hybrid biomembrane onto black phosphorus nanosheets (BP NSs) loaded with polymetformin (PolyMet) and fingolimod hydrochloride (FTY720). Microglia membrane facilitates inflammation-directed targeting to the injured brain regions, while…

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Topics & keywords

Topics

Keywords

Microglia
Nasal administration
Central nervous system
Mitochondrion
Drug delivery
Stroke (engine)
Mechanism (biology)
Ischemia

UN Sustainable Development Goals

Good health and well-being

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