Superparamagnetic iron oxide nanoparticles impair endothelial integrity and inhibit nitric oxide production
Superparamagnetic iron oxide nanoparticles impair endothelial integrity and inhibit nitric oxide production
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DOI：
10.1016/j.actbio.2014.07.027
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发表时间：
2014-11-01
影响因子：
9.7
通讯作者：
Kiemer, Alexandra K.
中科院分区：
文献类型：
--
作者：
Astanina, Ksenia;Simon, Yvette;Kiemer, Alexandra K.
超顺磁性氧化铁纳米粒子（SPION）在临床和实验上广泛用于多种体内应用，例如磁共振成像中的对比度增强、热疗和药物输送。生物医学应用要求颗粒具有明确的物理和化学性质，并且在生物介质中保持稳定。尽管细胞毒性作用较低，但与生物医学用途相关的浓度下 SPION 的不良反应尚未得到足够详细的研究。在目前的工作中，我们采用了 Endorem (R)，一种被批准作为静脉造影剂的葡聚糖稳定的 SPION，并将其作用与一组具有磁共振成像应用潜力的其他纳米颗粒进行了比较。与体内应用相关的浓度的 SPION 很快被内皮细胞吸收，并且没有表现出直接的细胞毒性。细胞阻抗传感测量表明，SPION（而不是 BaSO4/Gd 纳米颗粒）损害了内皮完整性，这一点通过内皮单层细胞间间隙形成的增加得到了证实。这些结构变化诱导亚细胞易位，抑制细胞保护和抗动脉粥样硬化酶内皮 NO 合酶，并减少 NO 产生。 SPION 不影响脂多糖诱导的巨噬细胞炎症性 NO 的产生。总之，我们的数据表明，SPION 在治疗相关剂量下可能会显着改变内皮完整性和功能，且不具有细胞毒性。 (C) 2014 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
Superparamagnetic iron oxide nanoparticles (SPION) are widely used both clinically and experimentally for diverse in vivo applications, such as contrast enhancement in magnetic resonance imaging, hyperthermia and drug delivery. Biomedical applications require particles to have defined physical and chemical properties, and to be stable in biological media. Despite a suggested low cytotoxic action, adverse reactions of SPION in concentrations relevant for biomedical use have not yet been studied in sufficient detail. In the present work we employed Endorem (R), dextran-stabilized SPION approved as an intravenous contrast agent, and compared its action to a set of other nanoparticles with potential for magnetic resonance imaging applications. SPION in concentrations relevant for in vivo applications were rapidly taken up by endothelial cells and exhibited no direct cytotoxicity. Electric cell impedance sensing measurements demonstrated that SPION, but not BaSO4/Gd nanoparticles, impaired endothelial integrity, as was confirmed by increased intercellular gap formation in endothelial monolayers. These structural changes induced the subcellular translocation and inhibition of the cytoprotective and anti-atherosclerotic enzyme endothelial NO-synthase and reduced NO production. Lipopolysaccharide-induced inflammatory NO production of macrophages was not affected by SPION. In conclusion, our data suggest that SPION might substantially alter endothelial integrity and function at therapeutically relevant doses, which are not cytotoxic. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.