Department of Otorhinolaryngology, Hannover Medical School, Hannover, Germany.
Cluster of Excellence 'Hearing 4 all', NIFE, Hannover, Germany.
PLoS One. 2018 May 15;13(5):e0196649. doi: 10.1371/journal.pone.0196649. eCollection 2018.
Despite the technological progress made with cochlear implants (CI), impedances and their diagnosis remain a focus of interest. Increases in impedance have been related to technical defects of the electrode as well as inflammatory and/or fibrosis along the electrode. Recent studies have demonstrated highly increased impedances as the result of corroded platinum (Pt) electrode contacts. This in vitro study examined the effects of Pt ions and compounds generated by corrosion of the electrode contacts of a human CI on cell metabolism. Since traces of solid Pt in surrounding cochlear tissues have been reported, the impact of commercially available Pt nanoparticles (Pt-NP, size 3 nm) on the cell culture model was also determined. For this purpose, the electrode contacts were electrically stimulated in a 0.5% aqueous NaCl solution for four weeks and the mass fraction of the platinum dissolute (Pt-Diss) was determined by mass spectrometry (ICP-MS). Metabolic activity of the murine fibroblasts (NIH 3T3) and the human neuroblastoma (SH-SY5Y) cells was determined using the WST-1 assay following exposure to Pt-Diss and Pt-NP. It was found that 5-50 μg/ml of the Pt-NP did not affect the viability of both cell types. In contrast, 100 μg/ml of the nanoparticles caused significant loss in metabolic activity. Furthermore, transmission electron microscopy (TEM) revealed mitochondrial swelling in both cell types indicating cytotoxicity. Additionally, TEM demonstrated internalized Pt-NP in NIH 3T3 cells in a concentration dependent manner, whereas endocytosis in SH-SY5Y cells was virtually absent. In comparison with the Pt-NP, the corrosion products (Pt-Diss) with concentrations between 1.64 μg/ml and 8.2 μg/ml induced cell death in both cell lines in a concentration dependent manner. TEM imaging revealed both mitochondrial disintegration and swelling of the endoplasmic reticulum, suggesting that Pt ions trigger cytotoxicity in both NIH 3T3 and SH-SY5Y cell lines by interacting with the respiratory chain.
尽管在人工耳蜗（CI）方面取得了技术进步，但阻抗及其诊断仍然是关注的焦点。阻抗的增加与电极的技术缺陷以及电极上的炎症和/或纤维化有关。最近的研究表明，由于腐蚀的铂（Pt）电极接触，阻抗会大幅增加。这项体外研究检查了由 CI 电极接触腐蚀产生的 Pt 离子和化合物对细胞代谢的影响。由于周围耳蜗组织中存在固体 Pt 痕迹的报道，因此还确定了商业上可用的 Pt 纳米颗粒（Pt-NP，尺寸为 3nm）对细胞培养模型的影响。为此，将电极接触在 0.5%的水溶液中进行电刺激四周围，通过质谱法（ICP-MS）确定溶解的铂质量分数（Pt-Diss）。用 WST-1 测定法在暴露于 Pt-Diss 和 Pt-NP 后，测定鼠成纤维细胞（NIH 3T3）和人神经母细胞瘤（SH-SY5Y）的代谢活性。结果发现，5-50μg/ml 的 Pt-NP 不会影响两种细胞类型的活力。相比之下，100μg/ml 的纳米颗粒会导致代谢活性显著丧失。此外，透射电子显微镜（TEM）显示两种细胞类型的线粒体肿胀，表明细胞毒性。此外，TEM 还以浓度依赖的方式证明了 NIH 3T3 细胞中内化的 Pt-NP，而 SH-SY5Y 细胞中的内吞作用几乎不存在。与 Pt-NP 相比，浓度在 1.64μg/ml 至 8.2μg/ml 之间的腐蚀产物（Pt-Diss）以浓度依赖的方式诱导两种细胞系中的细胞死亡。TEM 成像显示线粒体解体和内质网肿胀，这表明 Pt 离子通过与呼吸链相互作用在 NIH 3T3 和 SH-SY5Y 细胞系中引发细胞毒性。
