Synthesis of acid-stabilized iron oxide nanoparticles and comparison for targeting atherosclerotic plaques: evaluation by MRI, quantitative MPS, and TEM alternative to ambiguous Prussian blue iron staining.
Synthesis of acid-stabilized iron oxide nanoparticles and comparison for targeting atherosclerotic plaques: evaluation by MRI, quantitative MPS, and TEM alternative to ambiguous Prussian blue iron staining.
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DOI：
10.1016/j.nano.2015.01.002
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发表时间：
2015-07
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通讯作者：
Constantin Scharlach;Harald Kratz;F. Wiekhorst;C. Warmuth;J. Schnorr;G. Genter;M. Ebert;S. Mueller;Eyk Schellenberger
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文献类型：
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作者：
Constantin Scharlach;Harald Kratz;F. Wiekhorst;C. Warmuth;J. Schnorr;G. Genter;M. Ebert;S. Mueller;Eyk Schellenberger
为了进一步优化柠檬酸盐稳定的 VSOP（非常小的氧化铁颗粒，为 MR 血管造影而开发）来识别动脉粥样硬化斑块，我们在合成过程中使用其他八种酸来修饰其表面以实现静电稳定。这种方法保留了临床应用的有效生产。有 5 种颗粒适合研究 apoE−/− 小鼠斑块的靶向情况。通过离体 MRI、TEM 评估累积情况，并通过磁粉光谱 (MPS) 定量评估。柠檬酸 (VSOP)、依替膦酸、酒石酸和苹果酸涂层颗粒积聚在动脉粥样硬化斑块中，VSOP 积聚最高（注射剂量的 0.2‰）。目标是巨噬细胞和改变的内皮细胞的吞噬溶酶体。使用 VSOP 的体内 MRI 可以明确斑块识别。普鲁士蓝染色显示斑块中含有丰富的内源性铁，与颗粒铁无法区分。在 apoE−/− 小鼠中，VSOP 仍然是用于动脉粥样硬化斑块成像的最佳阴离子氧化铁颗粒。 MPS 可以对如此小的样本中的超顺磁性纳米颗粒进行定量。来自临床编辑动脉中易损斑块的存在对于预测急性冠状动脉事件非常重要。 VSOP（非常小的氧化铁颗粒，为磁共振血管造影而开发）已被证明在识别动脉粥样硬化斑块方面非常敏感。作者在此研究了合成过程中对 VSOP 表面的进一步修饰，并比较了它们的功效。
To further optimize citrate-stabilized VSOPs (very small iron oxide particles, developed for MR angiography) for identification of atherosclerotic plaques, we modified their surface during synthesis using eight other acids for electrostatic stabilization. This approach preserves effective production for clinical application. Five particles were suitable to be investigated in targeting plaques of apoE−/−mice. Accumulation was evaluated byex vivoMRI, TEM, and quantitatively by magnetic particle spectroscopy (MPS). Citric- (VSOP), etidronic-, tartaric-, and malic-acid-coated particles accumulated in atherosclerotic plaques with highest accumulation for VSOP (0.2‰ of injected dose). Targets were phagolysosomes of macrophages and of altered endothelial cells.In vivoMRI with VSOP allowed for definite plaque identification. Prussian blue staining revealed abundant endogenous iron in plaques, indistinguishable from particle iron. In apoE−/−mice, VSOPs are still the best anionic iron oxide particles for imaging atherosclerotic plaques. MPS allows for quantification of superparamagnetic nanoparticles in such small specimens.From the Clinical EditorThe presence of vulnerable plaques in arteries is important for the prediction of acute coronary events. VSOP (very small iron oxide particles, developed for MR angiography) have been shown to be very sensitive in identifying atherosclerotic plaques. The authors studied here further modification to the surface of VSOP during synthesis and compared their efficacy.