Iron-Doping of Copper Oxide Nanoparticles Lowers Their Toxic Potential on C6 Glioma Cells
Iron-Doping of Copper Oxide Nanoparticles Lowers Their Toxic Potential on C6 Glioma Cells
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DOI：
10.1007/s11064-020-02954-y
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发表时间：
2020-01
影响因子：
4.4
通讯作者：
Arundhati Joshi;H. Naatz;K. Faber;S. Pokhrel;R. Dringen
中科院分区：
文献类型：
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作者：
Arundhati Joshi;H. Naatz;K. Faber;S. Pokhrel;R. Dringen
氧化铜纳米颗粒（CuO-NP）因其细胞毒性而众所周知，这部分归因于铜离子从CuO-NP中的释放。由于已经报道了铁掺杂降低了CuO-NP对溶解的敏感性，我们比较了纯CuO-NP和掺杂有10%铁的CuO-NP（CuO-Fe-NP）的铜释放及其对C6胶质瘤细胞的毒性潜力。物理化学表征表明，二巯基琥珀酸酯（DMSA）包覆的CuO-NP和CuO-Fe-NP在它们的尺寸或zeta电位方面没有差异。然而，从CuO-Fe-NP的氧化还原活性和铜离子的释放与从CuO-NP的氧化还原活性和铜离子的释放相比显著较慢，如分别通过循环伏安法和通过铜离子-浴铜灵络合物的光度定量所证明的。C6细胞暴露于这些NP引起几乎相同的细胞铜积累，并且两种类型的NP中的每一种均诱导ROS产生和细胞毒性。然而，与暴露于CuO-Fe-NP的细胞相比，用CuO-NP处理的细胞的细胞活力的时间和浓度依赖性损失更严重。在铜螯合剂存在下，防止暴露于CuO-NP或CuO-Fe-NP后的铜积累和毒性，而通过巴弗洛霉素A1中和溶酶体pH防止毒性，而不影响细胞铜积累或ROS产生。这些数据表明，铁掺杂不影响CuO-NP的细胞积累，并表明铜离子从CuO-NP的细胞内释放被铁掺杂减慢，这反过来降低了铁掺杂的CuO-NP的细胞毒性潜力。
Copper oxide nanoparticles (CuO-NPs) are well known for their cytotoxicity which in part has been attributed to the release of copper ions from CuO-NPs. As iron-doping has been reported to reduce the susceptibility of CuO-NPs to dissolution, we have compared pure CuO-NPs and CuO-NPs that had been doped with 10% iron (CuO-Fe-NPs) for copper release and for their toxic potential on C6 glioma cells. Physicochemical characterization revealed that dimercaptosuccinate (DMSA)-coated CuO-NPs and CuO-Fe-NPs did not differ in their size or zeta potential. However, the redox activity and liberation of copper ions from CuO-Fe-NPs was substantially slower compared to that from CuO-NPs, as demonstrated by cyclic voltammetry and by the photometric quantification of the copper ion-bathocuproine complex, respectively. Exposure of C6 cells to these NPs caused an almost identical cellular copper accumulation and each of the two types of NPs induced ROS production and cell toxicity. However, the time- and concentration-dependent loss in cell viability was more severe for cells that had been treated with CuO-NPs compared to cells exposed to CuO-Fe-NPs. Copper accumulation and toxicity after exposure to either CuO-NPs or CuO-Fe-NPs was prevented in the presence of copper chelators, while neutralization of the lysosomal pH by bafilomycin A1 prevented toxicity without affecting cellular copper accumulation or ROS production. These data demonstrate that iron-doping does not affect cellular accumulation of CuO-NPs and suggests that the intracellular liberation of copper ions from CuO-NPs is slowed by the iron doping, which in turn lowers the cell toxic potential of iron-doped CuO-NPs.