Drug-carrying nanoparticles are a promising strategy to deliver therapeutics into the brain, but their translation requires better characterization of interactions between nanomaterials and endothelial cells of the blood–brain barrier (BBB). Here, we use a library of 18 layer-by-layer electrostatically assembled nanoparticles (NPs) to independently assess the impact of NP core and surface materials on in vitro uptake, transport, and intracellular trafficking in brain endothelial cells. We demonstrate that NP core stiffness determines the magnitude of transport, while surface chemistry directs intracellular trafficking. Finally, we demonstrate that these factors similarly dictate in vivo BBB transport using intravital imaging through cranial windows in mice. We identify that hyaluronic acid surface chemistry increases transport across the BBB in vivo, and flow conditions are necessary to replicate this finding in vitro. Taken together, these findings highlight the importance of assay geometry, cell biology, and fluid flow in developing nanocarriers for delivery to the brain.

中文翻译：

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通过血脑屏障的运输是由逐层纳米颗粒的核心和外表面成分引导的

载药纳米粒子是将治疗药物输送到大脑中的一种很有前途的策略，但其翻译需要更好地表征纳米材料和血脑屏障（BBB）内皮细胞之间的相互作用。在这里，我们使用 18 层静电组装纳米颗粒 (NP) 库来独立评估 NP 核心和表面材料对脑内皮细胞体外摄取、运输和细胞内运输的影响。我们证明纳米粒子核心硬度决定运输的程度，而表面化学指导细胞内运输。最后，我们通过小鼠颅窗活体成像证明这些因素同样决定体内 BBB 转运。我们发现透明质酸表面化学会增加体内跨血脑屏障的运输，并且流动条件对于在体外复制这一发现是必要的。总而言之，这些发现强调了测定几何学、细胞生物学和流体流动在开发用于递送至大脑的纳米载体中的重要性。