AbstractThe release of iron from iron nanoparticles (NPs) used as parenteral formulations appears to be influenced by the size and surface properties of the colloidal iron complex and the matrix. A clinically applied product Venofer® has been used as a model formulation to establish adequate analytical strategies to evaluate the fate of iron nanoparticles (NPs) in blood. First, the preparation was characterized by high resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS) and UV-vis absorption spectroscopy. This revealed the presence of monodisperse iron NPs with a hydrodynamic diameter of ∼15 nm and an iron core of ∼4 nm. Venofer® was then incubated with serum and whole blood in a quantitative study on the iron bioavailability from these NPs. Iron was speciated and quantified by using inductively coupled plasma mass spectrometry (ICP-MS). Iron solubilization levels of up to 42% were found in both fluids using isotope dilution of iron for quantification within the first hour of incubation even in the absence of the reticulo-endothelial system. The monitoring of the iron-containing proteins present in serum was conducted by high-performance liquid chromatography with ICP-MS detection. It indicated that the dissolved iron ions are bound to transferrin. Quantitative speciation studies using isotope pattern deconvolution experiments concluded that the released iron saturated almost completely (up to 90%) the metal binding sites of transferrin. The remaining iron appeared also associated to albumin and, to a lesser extent, forming smaller sized particles. Thus, the methods presented here provide new insights into the fate of Venofer® nanoparticles and may be applied to other formulations. Graphical abstractThe release of iron ions from sucrose covered iron nanoparticles used as parenteral formulations is evaluated in serum and whole blood by elemental mass spectrometry.

中文翻译：

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使用基于质谱的策略用于治疗血液中缺铁的铁纳米颗粒的命运

摘要铁纳米颗粒 (NPs) 中铁的释放似乎受到胶体铁复合物和基质的大小和表面性质的影响。临床应用的产品 Venofer® 已被用作模型配方，以建立适当的分析策略来评估血液中铁纳米粒子 (NP) 的命运。首先，通过高分辨率透射电子显微镜 (HR-TEM)、动态光散射 (DLS) 和紫外-可见吸收光谱对制备进行了表征。这表明存在流体动力学直径约为 15 nm 和铁核约为 4 nm 的单分散铁纳米颗粒。然后将 Venofer® 与血清和全血一起孵育，以定量研究这些纳米颗粒的铁生物利用度。使用电感耦合等离子体质谱法 (ICP-MS) 对铁进行形态分析和定量。即使在没有网状内皮系统的情况下，在孵育的第一小时内使用铁的同位素稀释进行定量，在两种流体中都发现了高达 42% 的铁溶解水平。血清中含铁蛋白质的监测是通过高效液相色谱与 ICP-MS 检测进行的。这表明溶解的铁离子与转铁蛋白结合。使用同位素模式解卷积实验的定量形态研究得出结论，释放的铁几乎完全（高达 90%）饱和转铁蛋白的金属结合位点。剩余的铁似乎也与白蛋白有关，并在较小程度上形成较小尺寸的颗粒。因此，这里介绍的方法提供了对 Venofer® 纳米粒子命运的新见解，并可应用于其他配方。图形摘要通过元素质谱法评估了血清和全血中用作肠胃外制剂的蔗糖覆盖的铁纳米颗粒中铁离子的释放。