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.

中文翻译：

---

体外血脑屏障模型中硫酸乙酰肝素蛋白聚糖介导的神经干细胞外泌体的动力依赖转运

血脑屏障（BBB）的存在极大地阻碍了药物向大脑的输送，血脑屏障（BBB）严格调节分子从血液到大脑的通道，反之亦然。可以封装药物的纳米载体可以通过胞吞作用穿过血脑屏障（BBB），从而显示出改善向大脑的药物输送的希望。在这里，我们演示了使用天然纳米囊泡，即来自C17.2神经干细胞（NSC）的外来体，有效地跨由人脑微血管内皮细胞组成的体外BBB模型携带蛋白质货物。我们显示，外泌体主要通过内吞作用吸收在脑内皮细胞中，而硫酸乙酰肝素蛋白聚糖（HSPG）充当受体。在一起 我们的数据支持以下观点：NSC外泌体可以充当生物纳米载体，从而有效地穿过血脑屏障。靶向HSPGs的纳米药物可能会改善其与脑内皮细胞的结合，并可能显示随后穿过血脑屏障的转胞作用。