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000284045 1001_ $$aYin, Yue$$b0
000284045 245__ $$aIntranasal blood-brain barrier bypass enables sequential mitochondria-targeted bioengineered nanolamellar system for ischemic stroke therapy.
000284045 260__ $$a[London]$$bSpringer Nature$$c2026
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000284045 520__ $$aMitochondrial damage constitutes the central pathological mechanism of cerebral ischemia-reperfusion (I/R) injury. Targeted delivery of antioxidants to mitochondria and the phenotype polarization of glial cells holds great promise for effective treatment. However, the blood-brain barrier (BBB) remains a major obstacle, causing insufficient drug accumulation in neuronal mitochondria. Here, we develop a bioengineered nanolamellar system (MM@BPPF) by coating microglia-mitochondria hybrid biomembrane onto black phosphorus nanosheets (BP NSs) loaded with polymetformin (PolyMet) and fingolimod hydrochloride (FTY720). Microglia membrane facilitates inflammation-directed targeting to the injured brain regions, while mitochondria membrane confers homotypic targeting to mitochondria. Meanwhile, BP NSs, PolyMet, and FTY720 act sequentially to restore mitochondrial function of neuronal cells and modulate microglial polarization. Intranasal administration enables MM@BPPF to bypass the BBB, substantially improving brain-targeting efficiency. This work not only offers an innovative sequential targeting strategy for mitigating I/R injury but also presents a potential paradigm for treating other central nervous system disorders.
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000284045 650_7 $$0G926EC510T$$2NLM Chemicals$$aFingolimod Hydrochloride
000284045 650_2 $$2MeSH$$aBlood-Brain Barrier: metabolism
000284045 650_2 $$2MeSH$$aBlood-Brain Barrier: drug effects
000284045 650_2 $$2MeSH$$aAnimals
000284045 650_2 $$2MeSH$$aMitochondria: metabolism
000284045 650_2 $$2MeSH$$aMitochondria: drug effects
000284045 650_2 $$2MeSH$$aMicroglia: metabolism
000284045 650_2 $$2MeSH$$aMicroglia: drug effects
000284045 650_2 $$2MeSH$$aMice
000284045 650_2 $$2MeSH$$aIschemic Stroke: drug therapy
000284045 650_2 $$2MeSH$$aIschemic Stroke: metabolism
000284045 650_2 $$2MeSH$$aIschemic Stroke: pathology
000284045 650_2 $$2MeSH$$aAdministration, Intranasal
000284045 650_2 $$2MeSH$$aFingolimod Hydrochloride: administration & dosage
000284045 650_2 $$2MeSH$$aFingolimod Hydrochloride: pharmacology
000284045 650_2 $$2MeSH$$aReperfusion Injury: drug therapy
000284045 650_2 $$2MeSH$$aMale
000284045 650_2 $$2MeSH$$aMice, Inbred C57BL
000284045 650_2 $$2MeSH$$aDrug Delivery Systems: methods
000284045 650_2 $$2MeSH$$aBioengineering
000284045 650_2 $$2MeSH$$aNeurons: drug effects
000284045 650_2 $$2MeSH$$aNeurons: metabolism
000284045 650_2 $$2MeSH$$aDisease Models, Animal
000284045 650_2 $$2MeSH$$aBrain: metabolism
000284045 650_2 $$2MeSH$$aBrain: drug effects
000284045 7001_ $$aLi, Zixuan$$b1
000284045 7001_ $$aShu, Weijie$$b2
000284045 7001_ $$aLiu, Hening$$b3
000284045 7001_ $$aWang, Zihan$$b4
000284045 7001_ $$aFu, Cong$$b5
000284045 7001_ $$aZhu, Yuanbo$$b6
000284045 7001_ $$aLi, Xuejing$$b7
000284045 7001_ $$aZhang, Yi$$b8
000284045 7001_ $$aLv, Bei$$b9
000284045 7001_ $$aWang, Zixuan$$b10
000284045 7001_ $$aZhao, Qiaoqiao$$b11
000284045 7001_ $$0P:(DE-2719)2813521$$aLiu, Dan$$b12
000284045 7001_ $$00000-0002-8598-7734$$aTang, Lu$$b13
000284045 7001_ $$0P:(DE-HGF)0$$aWang, Wei$$b14
000284045 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-68024-5$$gVol. 17, no. 1, p. 760$$n1$$p760$$tNature Communications$$v17$$x2041-1723$$y2026
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