Gupta Ruby, Chauhan Anjali, Kaur Tashmeen, Kuanr Bijoy K, Sharma Deepika
Institute of Nano Science and Technology, Knowledge City, Sector 81, Mohali, Punjab-140306, India.
Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi-110067, India.
Nanoscale. 2022 Dec 8;14(47):17589-17606. doi: 10.1039/d2nr02210a.
Despite advances in neurology, drug delivery to the central nervous system is considered a challenge due to the presence of the blood brain barrier (BBB). In this study, the role of magnetic hyperthermia induced by exposure of magnetic nanoparticles (MNPs) to an alternating magnetic field (AMF) in synergy with an external magnetic field (EMF) was investigated to transiently increase the permeability of the MNPs across the BBB. A dual magnetic targeting approach was employed by first dragging the MNPs by an EMF for an intended enhanced cellular association with the brain endothelial cells and then activating the MNPs by an AMF for the temporary disruption of the tight junctions of BBB. The efficacy of the BBB permeability for the MNPs under the influence of dual magnetic targeting was evaluated using transwell models developed by co-culturing murine brain endothelial cells with astrocytes, as well as in mouse models. The results revealed that the exposure to AMF transiently opened the tight junctions at the BBB, which, after 3 h of treatment, were observed to recover back to their comparable control levels. A biodistribution analysis of nanoparticles confirmed targeted accumulation of MNPs in the brain following dual targeting. This dual targeting approach was observed to open the tight junctions, thus increasing the transport of MNPs into the brain with higher specificity as compared to using EMF targeting alone, suggesting that a dual magnetic targeting-induced transport of MNPs across the BBB is an effective measure for delivery of therapeutics.
尽管神经学取得了进展，但由于血脑屏障（BBB）的存在，向中枢神经系统给药仍被视为一项挑战。在本研究中，研究了磁性纳米颗粒（MNPs）暴露于交变磁场（AMF）与外部磁场（EMF）协同作用下诱导的磁热疗在短暂增加MNPs跨血脑屏障通透性方面的作用。采用了双重磁靶向方法，首先通过外部磁场拖动MNPs，以增强其与脑内皮细胞的细胞结合，然后通过交变磁场激活MNPs，以暂时破坏血脑屏障的紧密连接。使用共培养小鼠脑内皮细胞和星形胶质细胞建立的Transwell模型以及小鼠模型，评估了双重磁靶向影响下MNPs的血脑屏障通透性功效。结果显示，暴露于交变磁场会使血脑屏障处的紧密连接暂时打开，在处理3小时后，观察到其恢复到与对照相当的水平。纳米颗粒的生物分布分析证实了双重靶向后脑内MNPs的靶向积累。与单独使用外部磁场靶向相比，观察到这种双重靶向方法可打开紧密连接，从而以更高的特异性增加MNPs向脑内的转运，这表明双重磁靶向诱导的MNPs跨血脑屏障转运是一种有效的治疗药物递送措施。
