Abstract

Among the available nanoparticles, those based on iron oxide are of particular interest due to their biological safety, magnetic properties, potential for imparting desired physico-chemical properties, and capacity for surface modifications with biocompatible, bioactive materials, ligands and antibodies. An important aspect of nanoparticles that determines their possibilities and range of clinical applications is their biocompatibility profile. Toxic effects can arise due to mechanisms mediated by reactive oxygen species (ROS); therefore, the development of nanoparticles intended for biomedical applications requires special attention to safety assessment in terms of the generation of oxidative stress. In this study, we examined the application of various shells (based on polylactide, polysaccharide, or albumin) on the dose-dependent effect of magnetite nanoparticles (MNPs) on the generation of ROS in stimulated human blood cells, as well as on the dynamics of the induced oxidative hemolysis of erythrocytes. MNPs with a shell of polylactide, albumin, and polysaccharide, in the range of all the used concentrations (0.1–2.0 mg/mL) and throughout the entire incubation period (0–180 min), did not affect the kinetics of the chemiluminescence response, while providing a unidirectional but differently pronounced decrease in the maximum intensity of induced chemiluminescence and total ROS production. All types of investigated nanoparticles in the range of concentrations from 1.0 to 2.0 mg/mL provided a dose-dependent enhancement of this effect. Under conditions of induced ROS generation, the various MNP shells did not modify the effects of these nanoparticles and only regulated their intensity. MNPs with a polylactide shell had a maximum effect.

中文翻译：

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具有各种壳修饰的基于氧化铁的纳米颗粒对体外刺激的人血细胞中活性氧种类的产生的影响

摘要

在可用的纳米粒子中，那些基于氧化铁的纳米粒子特别受关注，因为它们具有生物安全性、磁性、赋予所需物理化学特性的潜力以及用生物相容性、生物活性材料、配体和抗体进行表面修饰的能力。决定其临床应用的可能性和范围的纳米颗粒的一个重要方面是它们的生物相容性特征。由于活性氧 (ROS) 介导的机制，可能会产生毒性作用；因此，用于生物医学应用的纳米颗粒的开发需要特别注意氧化应激产生方面的安全评估。在这项研究中，我们研究了各种壳的应用（基于聚乳酸、多糖、或白蛋白）对磁铁矿纳米颗粒 (MNP) 对受刺激的人血细胞中 ROS 产生的剂量依赖性影响，以及对诱导的红细胞氧化溶血的动力学的影响。具有聚丙交酯、白蛋白和多糖外壳的 MNP，在所有使用的浓度范围内 (0.1–2.0 mg/mL) 和整个孵育期 (0–180 分钟)，不影响化学发光响应的动力学，同时在诱导化学发光的最大强度和总 ROS 产生方面提供单向但不同显着的降低。浓度范围为 1.0 至 2.0 mg/mL 的所有类型的研究纳米颗粒都提供了这种效应的剂量依赖性增强。在诱导 ROS 产生的条件下，各种 MNP 壳并没有改变这些纳米粒子的效果，只是调节了它们的强度。具有聚乳酸外壳的 MNP 具有最大的效果。