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

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 mitochondria membrane confers homotypic targeting to mitochondria. Meanwhile, BP N

SUBMITTER: Yin Y 

PROVIDER: S-EPMC12820287 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature