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Nano Lett. 2019 Feb 27. doi: 10.1021/acs.nanolett.8b04148. [Epub ahead of print]

Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders.

Author information

1
Sagol School of Neuroscience , Tel Aviv University , Tel Aviv 6997801 , Israel.
2
Sacklar School of Medicine, Department of Human Genetics and Biochemistry , Tel Aviv University , Tel Aviv 6997801 , Israel.
3
Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials , Bar-Ilan University , Ramat Gan 5290002 , Israel.
4
School of Neurobiology, Biochemistry and Biophysics, Life Sciences Faculty , Tel Aviv University , Tel Aviv 6997801 , Israel.

Abstract

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.

KEYWORDS:

Exosomes; drug delivery; gold nanoparticals; neurodegeneration; neuroimaging; neuroinflammation

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