Brain tumor targeting of magnetic nanoparticles for potential drug delivery: effect of administration route and magnetic field topography.
Brain tumor targeting of magnetic nanoparticles for potential drug delivery: effect of administration route and magnetic field topography.
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DOI：
10.1016/j.jconrel.2011.06.033
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发表时间：
2011-11-07
期刊：
影响因子：
--
通讯作者：
Yang VC
中科院分区：
文献类型：
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作者：
Chertok B;David AE;Yang VC
我们之前的研究证明了血管内给药后磁介导的氧化铁纳米粒子在脑肿瘤中保留的可行性。本研究的目的是阐明进一步改进这种有希望的方法的策略。特别是，我们探索了通过非闭塞的颈动脉施用纳米颗粒，作为增加肿瘤脉管系统对纳米颗粒的被动暴露以进行随后的磁性捕获的一种方法。然而，纳米粒子在传入脉管系统中的聚集干扰了肿瘤靶向。我们的实验中采用的磁性装置被发现在较宽的范围内产生相对均匀的磁通密度，使传入脉管系统区域暴露于高磁力下。为了克服这个问题，使用直径为 9 毫米的圆柱形 NdFeB 磁铁修改了磁性设置，以表现出更陡峭的磁场形貌。通过这种修改，注射部位的磁力减少了六倍，缓解了颈动脉血流完好的情况下的聚集问题。使用这种设置，发现与静脉内途径相比，350 mT 的颈动脉给药在神经胶质瘤中的纳米颗粒积累增加了 1.8 倍。发现这种增加与理论上估计的颈动脉给药 Rd 的 1.9 倍优势相当一致。当应用于具有更高 Rd 值的载药纳米粒子时，预计所开发的方法将呈现出更大的优势。
Our previous studies demonstrated feasibility of magnetically-mediated retention of iron-oxide nanoparticles in brain tumors after intravascular administration. The purpose of this study was to elucidate strategies for further improvement of this promising approach. In particular, we explored administration of the nanoparticles via a non-occluded carotid artery as a way to increase the passive exposure of tumor vasculature to nanoparticles for subsequent magnetic entrapment. However, aggregation of nanoparticles in the afferent vasculature interfered with tumor targeting. The magnetic setup employed in our experiments was found to generate a relatively uniform magnetic flux density over a broad range, exposing the region of the afferent vasculature to high magnetic force. To overcome this problem, the magnetic setup was modified with a 9-mm diameter cylindrical NdFeB magnet to exhibit steeper magnetic field topography. Six-fold reduction of the magnetic force at the injection site, achieved with this modification, alleviated the aggregation problem under the conditions of intact carotid blood flow. Using this setup, carotid administration was found to present 1.8-fold increase in nanoparticle accumulation in glioma compared to the intravenous route at 350 mT. This increase was found to be in reasonable agreement with the theoretically estimated 1.9-fold advantage of carotid administration, Rd. The developed approach is expected to present an even greater advantage when applied to drug-loaded nanoparticles exhibiting higher values of Rd.