Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders

Exosomes, nanovesicles that are secreted by different cell types, enable intercellular communication at local or distant sites. Alhough they have been found to cross the blood brain barrier, their migration and homing abilities within the brain remain unstudied. We have recently developed a method f...

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Bibliographic Details
Published in:Nano letters 2019-06, Vol.19 (6), p.3422-3431
Main Authors: Perets, Nisim, Betzer, Oshra, Shapira, Ronit, Brenstein, Shmuel, Angel, Ariel, Sadan, Tamar, Ashery, Uri, Popovtzer, Rachela, Offen, Daniel
Format: Article
Language:English
Subjects:
Alzheimer Disease - diagnostic imaging
Animals
Brain - diagnostic imaging
Disease Models, Animal
Exosomes - chemistry
Gold - analysis
Mesenchymal Stem Cells - chemistry
Metal Nanoparticles - analysis
Neurodegenerative Diseases - diagnostic imaging
Neurodevelopmental Disorders - diagnostic imaging
Neuroimaging - methods
Tomography, X-Ray Computed - methods
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Summary:Exosomes, nanovesicles that are secreted by different cell types, enable intercellular communication at local or distant sites. Alhough they have been found to cross the blood brain barrier, their migration and homing abilities within the brain remain unstudied. We have recently developed a method for longitudinal and quantitative in vivo neuroimaging of exosomes based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with gold nanoparticles as labeling agents. Here, we used this technique to track the migration and homing patterns of intranasally administrated exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) in different brain pathologies, including stroke, autism, Parkinson’s disease, and Alzheimer’s disease. We found that MSC-exo specifically targeted and accumulated in pathologically relevant murine models brains regions up to 96 h post administration, while in healthy controls they showed a diffuse migration pattern and clearance by 24 h. The neuro-inflammatory signal in pathological brains was highly correlated with MSC-exo accumulation, suggesting that the homing mechanism is inflammatory-driven. In addition, MSC-exo were selectively uptaken by neuronal cells, but not glial cells, in the pathological regions. Taken together, these findings can significantly promote the application of exosomes for therapy and targeted drug delivery in various brain pathologies.
ISSN:1530-6984
1530-6992
DOI:10.1021/acs.nanolett.8b04148