Balas Mihaela, Iconaru Simona Liliana, Dinischiotu Anca, Buton Nicolas, Predoi Daniela
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania.
HORIBA Jobin Yvon S.A.S., 6-18, Rue du Canal, CEDEX, 91165 Longjumeau, France.
Pharmaceutics. 2023 Feb 7;15(2):552. doi: 10.3390/pharmaceutics15020552.
Presently, iron oxide nanoparticles are the only ones approved for clinical use as contrast agents in magnetic resonance imaging (MRI). Even though there is a high demand for these types of nanoparticles both for clinical use as well as for research, there are difficulties in obtaining stable nanoparticles with reproducible properties. In this context, in this study, we report the obtaining by an adapted coprecipitation method of dextran-coated maghemite nanoparticles (ɤ-FeO NPs). The morphology and structure of the dextran-coated maghemite nanoparticles (ɤ-FeO NPs) were determined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The TEM and SEM micrographs highlighted the obtaining of particles of nanometric size and spherical shape morphology. Furthermore, the high-resolution transmission electron microscopy (HRTEM), as well as selected area diffraction (SAED), revealed that the obtained samples presented the structure of cubic maghemite. In this study, we also explored the effects of the co-precipitation synthesized dextran-coated maghemite nanoparticles (ɤ-FeO NPs) on the redox status of macrophages. For cytotoxicity evaluation of these NPs, murine macrophages (RAW 264.7 cell line) were exposed to different concentrations of dextran-coated maghemite nanoparticles (ɤ-FeO NPs) corresponding to 0-500 μg Fe/mL and incubated for 24, 48, and 72 h. Intracellular iron uptake, changes in the oxidative stress parameters (reactive oxygen species production and malondialdehyde level), and the activity of antioxidant enzymes, as well as GSH concentration in cells, were evaluated after incubation with a lower (50 μg Fe/mL) and higher (500 μg Fe/mL) dose of NPs. The results indicated a significant decrease in RAW 264.7 cell viability after 72 h in the presence of NPs at concentrations above 25 μg Fe/mL. An important accumulation of NPs, dependent on dose and exposure time, was detected in macrophages, but it induced only a limited raise in the oxidative status. We showed here that the antioxidant capacity of RAW 264.7 macrophages was efficient in counteracting dextran-coated maghemite nanoparticles (ɤ-FeO NPs) toxicity even at higher doses.
目前，氧化铁纳米颗粒是唯一被批准用于磁共振成像（MRI）临床的造影剂。尽管这类纳米颗粒在临床应用和研究方面都有很高的需求，但要获得具有可重复性质的稳定纳米颗粒仍存在困难。在此背景下，在本研究中，我们报告了通过改良共沉淀法获得葡聚糖包被的磁赤铁矿纳米颗粒（ɤ-FeO NPs）。使用扫描电子显微镜（SEM）和透射电子显微镜（TEM）确定了葡聚糖包被的磁赤铁矿纳米颗粒（ɤ-FeO NPs）的形态和结构。TEM和SEM显微照片突出显示获得了纳米尺寸且呈球形形态的颗粒。此外，高分辨率透射电子显微镜（HRTEM）以及选区衍射（SAED）表明，所得样品呈现出立方磁赤铁矿结构。在本研究中，我们还探讨了共沉淀合成的葡聚糖包被的磁赤铁矿纳米颗粒（ɤ-FeO NPs）对巨噬细胞氧化还原状态的影响。为了评估这些纳米颗粒的细胞毒性，将小鼠巨噬细胞（RAW 264.7细胞系）暴露于对应0 - 500 μg Fe/mL的不同浓度葡聚糖包被的磁赤铁矿纳米颗粒（ɤ-FeO NPs）中，并孵育24、48和72小时。在用较低（50 μg Fe/mL）和较高（500 μg Fe/mL）剂量的纳米颗粒孵育后，评估细胞内铁摄取、氧化应激参数（活性氧产生和丙二醛水平）的变化、抗氧化酶活性以及细胞内谷胱甘肽浓度。结果表明，在浓度高于25 μg Fe/mL的纳米颗粒存在下，72小时后RAW 264.7细胞活力显著下降。在巨噬细胞中检测到纳米颗粒的重要积累，其依赖于剂量和暴露时间，但仅引起氧化状态的有限升高。我们在此表明，即使在较高剂量下，RAW 264.7巨噬细胞的抗氧化能力也能有效抵消葡聚糖包被的磁赤铁矿纳米颗粒（ɤ-FeO NPs）的毒性。
