Magnetic targeting of nanoparticles across the intact blood-brain barrier.

Magnetic targeting of nanoparticles across the intact blood-brain barrier.
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DOI:
10.1016/j.jconrel.2012.09.021
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发表时间:
2012-11-28
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Jin S
Jin S
中科院分区:
其他
文献类型:
--
作者:
Kong SD;Lee J;Ramachandran S;Eliceiri BP;Shubayev VI;Lal R;Jin S

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通过完整的血脑屏障(BBB)输送治疗或诊断药物仍然是一个重大挑战。在这里,我们在一个小鼠模型中演示了磁性纳米颗粒(MNPs)在受到外部磁场的作用下可以穿过正常的血脑屏障。全身给药后,外加磁场调节MNPs穿透血脑屏障并在脑实质血管周围积聚的能力。使用荧光MNPs建立了体内血管内皮细胞内和血管周围细胞外基质的直接跟踪和定位。这些MNPs是惰性的,与低毒相关,使用非侵入性报告进行星形胶质细胞增生、生化和组织学研究。原子力显微镜显示MNPs被内皮细胞内化,提示跨细胞转运可能是MNP跨越血脑屏障的一种机制。二氧化硅包裹的磁性纳米胶囊(SiMNC)允许通过远程射频(RF)磁场按需释放药物。总而言之,这些结果建立了一种有效的策略,通过应用外部磁场来调节MNPs在大脑中的生物分布。
Delivery of therapeutic or diagnostic agents across an intact blood–brain barrier (BBB) remains a major challenge. Here we demonstrate in a mouse model that magnetic nanoparticles (MNPs) can cross the normal BBB when subjected to an external magnetic field. Following a systemic administration, an applied external magnetic field mediates the ability of MNPs to permeate the BBB and accumulate in a perivascular zone of the brain parenchyma. Direct tracking and localization inside endothelial cells and in the perivascular extracellular matrix in vivo was established using fluorescent MNPs. These MNPs were inert and associated with low toxicity, using a non-invasive reporter for astrogliosis, biochemical and histological studies. Atomic force microscopy demonstrated that MNPs were internalized by endothelial cells, suggesting that trans-cellular trafficking may be a mechanism for the MNP crossing of the BBB observed. The silica-coated magnetic nanocapsules (SiMNCs) allow on-demand drug release via remote radio frequency (RF) magnetic field. Together, these results establish an effective strategy for regulating the biodistribution of MNPs in the brain through the application of an external magnetic field.
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