Receptor-Mediated Delivery of Magnetic Nanoparticles across the Blood-Brain Barrier
Receptor-Mediated Delivery of Magnetic Nanoparticles across the Blood-Brain Barrier
复制标题
受体介导的磁性纳米颗粒穿过血脑屏障的递送
DOI：
10.1021/nn300240p
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发表时间：
2012-04-01
期刊：
影响因子：
17.1
通讯作者：
Gao, Mingyuan
中科院分区：
文献类型：
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作者：
Qiao, Ruirui;Jia, Qiaojuan;Gao, Mingyuan
将乳铁蛋白(LF)共价连接到聚乙二醇包覆的Fe3O4纳米粒子上，通过存在于脑内皮细胞上的乳铁蛋白受体介导的跨细胞转运，促进纳米粒子通过血脑屏障(BBB)的转运。采用血脑屏障细胞培养模型和SD大鼠体内实验，评价Fe3O4-LF结合物跨越血脑屏障的效果。在体外实验中，使用了一种成熟的猪血脑屏障模型，该模型基于生长在过滤器支架上的脑毛细血管内皮细胞的原代培养，从而使人们能够跟踪纳米颗粒从顶端(血液)到基底外侧(大脑)的转移。对于体内实验，以SD大鼠为动物模型，利用MRI技术检测纳米颗粒通过血脑屏障的情况。体外和体内实验结果表明，与聚乙二醇包被的Fe3O4纳米粒子相比，Fe3O4-LF探针具有更强的穿透血脑屏障的能力，进一步表明LF受体介导的细胞转运是一种有效的跨血脑屏障转运手段。
A brain delivery probe was prepared by covalently conjugating lactoferrin (Lf) to a poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticle in order to facilitate the transport of the nanoparticles across the blood-brain barrier (BBB) by receptor-mediated transcytosis via the Lf receptor present on cerebral endothelial cells. The efficacy of the Fe3O4-Lf conjugate to cross the BBB was evaluated in vitro using a cell culture model for the blood-brain barrier as well as in vivo in SD rats. For an in vitro experiment, a well-established porcine BBB model was used based on the primary culture of cerebral capillary endothelial cells grown on filter supports, thus allowing one to follow the transfer of nanoparticles from the apical (blood) to the basolateral (brain) side. For in vivo experiments, SD rats were used as animal model to detect the passage of the nanoparticles through the BBB by MRI techniques. The results of both in vitro and in vivo experiments revealed that the Fe3O4-Lf probe exhibited an enhanced ability to cross the BBB in comparison to the PEG-coated Fe3O4 nanoparticles and further suggested that the Lf-receptor-mediated transcytosis was an effective measure for delivering the nanoparticles across the BBB.