Lamson Nicholas G, Pickering Andrew J, Wyckoff Jeffrey, Ganesh Priya, Calle Elizabeth A, Straehla Joelle P, Hammond Paula T
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology Cambridge Massachusetts USA.
Department of Chemical Engineering Massachusetts Institute of Technology Cambridge Massachusetts USA.
Bioeng Transl Med. 2023 Dec 28;9(4):e10636. doi: 10.1002/btm2.10636. eCollection 2024 Jul.
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.
载药纳米颗粒是将治疗药物输送到大脑的一种很有前景的策略，但其转化应用需要更好地表征纳米材料与血脑屏障（BBB）内皮细胞之间的相互作用。在此，我们使用一个由18种逐层静电组装纳米颗粒（NP）组成的文库，独立评估NP核心和表面材料对脑内皮细胞体外摄取、转运及细胞内运输的影响。我们证明，NP核心硬度决定转运程度，而表面化学性质指导细胞内运输。最后，我们通过对小鼠颅骨窗口进行活体成像证明，这些因素同样决定体内BBB转运。我们发现，透明质酸表面化学性质可增加体内BBB的转运，且流动条件对于在体外重现这一发现是必要的。综上所述，这些发现突出了在开发用于脑部给药的纳米载体时，检测几何形状、细胞生物学和流体流动的重要性。
