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Heparan sulfate proteoglycan‐mediated dynamin‐dependent transport of neural stem cell exosomes in an in vitro blood–brain barrier model

2020/09/16 by Bhagyashree S. Joshi, Inge S. Zuhorn
Biochemistry, Genetics and Molecular Biology · #Extracellular vesicles in disease #MicroRNA in disease regulation #RNA Interference and Gene Delivery

paper · pdf · doi:10.1111/ejn.14974

openalex publication_date 2020/09/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30

Abstract

Drug delivery to the brain is greatly hampered by the presence of the blood-brain barrier (BBB) which tightly regulates the passage of molecules from blood to brain and vice versa. Nanocarriers, in which drugs can be encapsulated, can move across the blood-brain barrier (BBB) via the process of transcytosis, thus showing promise to improve drug delivery to the brain. Here, we demonstrate the use of natural nanovesicles, that is, exosomes, derived from C17.2 neural stem cells (NSCs) to efficiently carry a protein cargo across an in vitro BBB model consisting of human brain microvascular endothelial cells. We show that the exosomes are primarily taken up in brain endothelial cells via endocytosis, while heparan sulfate proteoglycans (HSPGs) act as receptors. Taken together, our data support the view that NSC exosomes may act as biological nanocarriers for efficient passage across the BBB. Nanomedicines that target HSPGs may improve their binding to brain endothelial cells and, possibly, show subsequent transcytosis across the BBB.

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