Kumarasamy Murali, Sosnik Alejandro
Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion-Israel Institute of Technology, De-Jur Bldg. Office 607, Technion City, 3200003 Haifa, Israel.
iScience. 2021 Feb 12;24(3):102183. doi: 10.1016/j.isci.2021.102183. eCollection 2021 Mar 19.
Nanoneuromedicine investigates nanotechnology to target the brain and treat neurological diseases. In this work, we biofabricated heterocellular spheroids comprising human brain microvascular endothelial cells, brain vascular pericytes and astrocytes combined with primary cortical neurons and microglia isolated from neonate rats. The structure and function are characterized by confocal laser scanning and light sheet fluorescence microscopy, electron microscopy, western blotting, and RNA sequencing. The spheroid bulk is formed by neural cells and microglia and the surface by endothelial cells and they upregulate key structural and functional proteins of the blood-brain barrier. These cellular constructs are utilized to preliminary screen the permeability of polymeric, metallic, and ceramic nanoparticles (NPs). Findings reveal that penetration and distribution patterns depend on the NP type and that microglia would play a key role in this pathway, highlighting the promise of this platform to investigate the interaction of different nanomaterials with the central nervous system in nanomedicine, nanosafety and nanotoxicology.
纳米神经医学研究利用纳米技术靶向大脑并治疗神经疾病。在这项工作中，我们生物制造了异细胞球体，其包含人脑血管内皮细胞、脑血管周细胞和星形胶质细胞，并结合了从新生大鼠分离的原代皮质神经元和小胶质细胞。通过共聚焦激光扫描和光片荧光显微镜、电子显微镜、蛋白质免疫印迹和RNA测序对其结构和功能进行了表征。球体主体由神经细胞和小胶质细胞形成，表面由内皮细胞形成，并且它们上调血脑屏障的关键结构和功能蛋白。这些细胞构建体用于初步筛选聚合物、金属和陶瓷纳米颗粒（NP）的渗透性。研究结果表明，穿透和分布模式取决于NP类型，并且小胶质细胞在该途径中起关键作用，突出了该平台在纳米医学、纳米安全性和纳米毒理学中研究不同纳米材料与中枢神经系统相互作用的前景。
