Innovative nanotechnology aims to develop particles that are small, monodisperse, smart, and do not cause unintentional side effects. Uniform magnetic Fe3O4 nanoparticles (12 nm in size) were prepared by thermal decomposition of iron(III) oleate. To make them colloidally stable and dispersible in water and cell culture medium, they were modified with phosphonic acid- (PA) and hydroxamic acid (HA)-terminated poly(ethylene glycol) yielding PA-PEG@Fe3O4 and HA-PEG@Fe3O4 nanoparticles; conventional γ-Fe2O3 particles were prepared as a control. Advanced techniques were used to evaluate the properties and safety of the particles. Completeness of the nanoparticle coating was tested by real-time polymerase chain reaction. Interaction of the particles with primary human peripheral blood cells, cellular uptake, cytotoxicity, and immunotoxicity were also investigated. Amount of internalized iron in peripheral blood mononuclear cells was 72, 38, and 25 pg Fe/cell for HA-PEG@Fe3O4, γ-Fe2O3, and PA-PEG@Fe3O4, respectively. Nanoparticles were localized within the cytoplasm and in the extracellular space. No cytotoxic effect of both PEGylated nanoparticles was observed (0.12-75 μg/cm2) after 24 and 72-h incubation. Moreover, no suppressive effect was found on the proliferative activity of T-lymphocytes and T-dependent B-cell response, phagocytic activity of monocytes and granulocytes, and respiratory burst of phagocytes. Similarly, no cytotoxic effect of γ-Fe2O3 particles was observed. However, they suppressed the proliferative activity of T-lymphocytes (75 μg/cm2, 72 h) and also decreased the phagocytic activity of monocytes (15 μg/cm2, 24 h; 3-75 μg/cm2, 72 h). We thus show that newly developed particles have great potential especially in cancer diagnostics and therapy.

中文翻译：

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纳米药物的单分散聚乙二醇化磁性纳米颗粒的毒性评估。

创新的纳米技术旨在开发小，单分散，智能且不会引起意外副作用的颗粒。通过油酸铁（III）的热分解制备均匀的磁性Fe3O4纳米颗粒（尺寸为12 nm）。为使它们胶体稳定并在水和细胞培养基中分散，将它们用膦酸-（PA）和异羟肟酸（HA）封端的聚乙二醇改性，得到PA-PEG @ Fe3O4和HA-PEG @ Fe3O4纳米颗粒; 制备常规的γ-Fe2 O 3颗粒作为对照。先进的技术被用来评估颗粒的性质和安全性。通过实时聚合酶链反应测试了纳米颗粒涂层的完整性。颗粒与人类原代外周血细胞的相互作用，细胞摄取，细胞毒性，和免疫毒性也进行了调查。对于HA-PEG @ Fe3O4，γ-Fe2O3和PA-PEG @ Fe3O4，外周血单核细胞中内在铁的含量分别为72、38和25 pg Fe /细胞。纳米颗粒位于细胞质内和细胞外空间。孵育24和72小时后，未观察到两种PEG化纳米颗粒的细胞毒性作用（0.12-75μg/ cm2）。此外，未发现对T淋巴细胞的增殖活性和T依赖性B细胞应答，单核细胞和粒细胞的吞噬活性以及吞噬细胞的呼吸爆发没有抑制作用。同样，没有观察到γ-Fe2O3颗粒的细胞毒性作用。然而，它们抑制了T淋巴细胞的增殖活性（75μg/ cm2，72 h），并且还降低了单核细胞的吞噬活性（15μg/ cm2，24 h； 3-75μg/ cm2，72 h）。