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Engineering extracellular vesicles to transiently permeabilize the blood-brain barrier
Francesca Tomatis1,2,3, Susana Rosa1,2, Susana Simões1,2
1CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, UC-Biotech Parque Tecnológico de Cantanhede, Coimbra, Portugal.
Journal of Nanobiotechnology
|December 2, 2024
Summary
Aging-associated small extracellular vesicles (sEVs) can temporarily open the blood-brain barrier (BBB). These miRNA-enriched sEVs offer a novel strategy for enhanced brain drug delivery.
Area of Science:
- Neuroscience
- Biotechnology
- Drug Delivery
Background:
- The blood-brain barrier (BBB) restricts drug entry into the brain.
- Physiological aging increases BBB permeability, influenced by blood factors like extracellular vesicles (EVs).
- Aging mechanisms offer insights for transient BBB opening strategies.
Purpose of the Study:
- To investigate the potential of small EVs (sEVs) enriched with aging-associated microRNAs (miRNAs) to transiently open the BBB.
- To evaluate the impact of these miRNA-enriched sEVs on BBB permeability in vitro.
Main Methods:
- Collected and analyzed sEVs from aged individuals to identify overexpressed miRNAs.
- Utilized a human in vitro BBB model under static and dynamic flow conditions.
- Assessed BBB permeability changes and molecular targets (claudin 5, ATF4) following sEV treatment.
Main Results:
- Aging-associated sEVs, particularly those enriched with miR-383-3p, significantly increased BBB permeability.
- This increased permeability was reversible and linked to decreased claudin 5 expression in brain endothelial cells.
- The mechanism involved, in part, the knockdown of activating transcription factor 4 (ATF4).
Conclusions:
- Engineered sEVs show promise for temporary BBB opening.
- This approach facilitates drug delivery to the brain via bloodstream injection.
- Leveraging aging-associated EVs offers a novel therapeutic strategy for brain-targeted drug delivery.
