Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan City 33302, Taiwan, ROC.
Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Guishan, Taoyuan City 33302, Taiwan, ROC.
Int J Nanomedicine. 2019 Jul 3;14:4767-4780. doi: 10.2147/IJN.S204844. eCollection 2019.
Magnetic nanoparticles (MNPs) can be localized against hemodynamic forces in blood vessels with the application of an external magnetic field. In addition, PEGylation of nanoparticles may increase the half-life of nanocomposites in circulation. In this work, we examined the effect of PEGylation on the magnetic capture of MNPs in vivo.
Laser speckle contrast imaging and capillaroscopy were used to assess the magnetic capture of dextran-coated MNPs and red blood cell (RBC) flow in cremaster microvessels of anesthetized rats. Magnetic capture of MNPs in serum flow was visualized with an in vitro circulating system. The effect of PEGylation on MNP-endothelial cell interaction was studied in cultured cells using an iron assay.
In microcirculation through cremaster muscle, magnet-induced retention of 250 nm MNPs was associated with a variable reduction in RBC flow, suggesting a dynamic coupling of hemodynamic and magnetic forces. After magnet removal, faster restoration of flow was observed in PEG(+) than PEG(-) group, which may be attributed to a reduced interaction with vascular endothelium. However, PEGylation appears to be required for magnetic capture of 50 nm MNPs in microvessels, which was associated with increased hydrodynamic diameter to 130±6 nm in serum, but independent of the ς-potential.
These results suggest that PEGylation may enhance magnetic capture of smaller MNPs and dispersion of larger MNPs after magnet removal, which may potentially affect the targeting, pharmacokinetics and therapeutic efficacy.
在外磁场的作用下，磁性纳米粒子（MNPs）可以在血管中对抗血流动力定位。此外，纳米粒子的聚乙二醇（PEG）化可能会增加纳米复合材料在循环中的半衰期。在这项工作中，我们研究了 PEG 化对 MNPs 在体内磁性捕获的影响。
激光散斑对比成像和毛细血管镜用于评估葡聚糖包覆的 MNPs 和麻醉大鼠的提睾肌微血管中红细胞（RBC）流动的磁性捕获。体外循环系统用于可视化血清流动中的 MNPs 磁性捕获。使用铁测定法研究了 PEG 化对培养细胞中 MNP-内皮细胞相互作用的影响。
在提睾肌微循环中，磁诱导保留 250nm 的 MNPs 与 RBC 流动的可变减少有关，这表明血流动力和磁场之间存在动态耦合。去除磁铁后，PEG（+）组比 PEG（-）组观察到更快的血流恢复，这可能归因于与血管内皮的相互作用减少。然而，PEG 化似乎是在微血管中捕获 50nm 的 MNPs 所必需的，这与血清中增加的水动力直径至 130±6nm 有关，但与ζ-电位无关。
这些结果表明，PEG 化可能增强较小 MNPs 的磁性捕获和较大 MNPs 在磁铁去除后的分散，这可能会影响靶向、药代动力学和治疗效果。
