Back to Search
Start Over
Targeted mRNA Nanoparticles Ameliorate Blood-Brain Barrier Disruption Postischemic Stroke by Modulating Microglia Polarization.
- Source :
-
ACS nano [ACS Nano] 2024 Jan 30; Vol. 18 (4), pp. 3260-3275. Date of Electronic Publication: 2024 Jan 16. - Publication Year :
- 2024
-
Abstract
- The ischemic stroke is a major global health concern, with high mortality and disability rates. Unfortunately, there is a dearth of effective clinical interventions for managing poststroke neuroinflammation and blood-brain barrier (BBB) disruption that are crucial for the brain injury evolving and neurological deficits. By leveraging the pathological progression of an ischemic stroke, we developed an M2 microglia-targeting lipid nanoparticle (termed MLNP) approach that can selectively deliver mRNA encoding phenotype-switching interleukin-10 (m IL-10 ) to the ischemic brain, creating a beneficial feedback loop that drives microglial polarization toward the protective M2 phenotypes and augments the homing of m IL-10 -loaded MLNPs (m IL-10 @MLNPs) to ischemic regions. In a transient middle cerebral artery occlusion (MCAO) mouse model of an ischemic stroke, our findings demonstrate that intravenously injected m IL-10 @MLNPs induce IL-10 production and enhance the M2 polarization of microglia. The resulting positive loop reinforces the resolution of neuroinflammation, restores the impaired BBB, and prevents neuronal apoptosis after stroke. Using a permanent distal MCAO mouse model of an ischemic stroke, the neuroprotective effects of m IL-10 @MLNPs have been further validated by the attenuation of the sensorimotor and cognitive neurological deficits. Furthermore, the developed mRNA-based targeted therapy has great potential to extend the therapeutic time window at least up to 72 h poststroke. This study depicts a simple and versatile LNP platform for selective delivery of mRNA therapeutics to cerebral lesions, showcasing a promising approach for addressing an ischemic stroke and associated brain conditions.
Details
- Language :
- English
- ISSN :
- 1936-086X
- Volume :
- 18
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- ACS nano
- Publication Type :
- Academic Journal
- Accession number :
- 38227975
- Full Text :
- https://doi.org/10.1021/acsnano.3c09817