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 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.