Quantitative Evaluation of Cisplatin Uptake in Sensitive and Resistant Individual Cells by Single-Cell ICP-MS (SC-ICP-MS)
Quantitative Evaluation of Cisplatin Uptake in Sensitive and Resistant Individual Cells by Single-Cell ICP-MS (SC-ICP-MS)
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DOI：
10.1021/acs.analchem.7b02746
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发表时间：
2017-11-07
影响因子：
7.4
通讯作者：
Montes-Bayon, M.
中科院分区：
文献类型：
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作者：
Corte Rodriguez, M.;Alvarez-Fernandez Garcia, R.;Montes-Bayon, M.
铂治疗癌症的主要局限性之一是相关耐药性的产生，这可能与细胞内铂浓度的显著降低有关。因此，细胞内铂浓度可作为顺铂耐药的生物标志物。在这项工作中，探索了一种解决单个细胞内铂浓度的替代方法，以允许以相对快速的方式评估不同的细胞模型和替代疗法。为此，使用总消耗雾化器与电感耦合等离子体质谱仪(ICPMS)联用，实现了单电池中总铂的分析。结合流式细胞术对该装置的效率进行了评估，结果表明效率约为25%(细胞从悬浮液中的细胞进入电感耦合等离子体质谱仪)。对单个细胞对一种无毒的含Tb化合物进行了定量摄取研究，并将结果与相同细胞的整体分析结果进行了比较。这两组数据在统计上具有可比性。因此，开发的方法学最终应用于顺铂耐药和敏感细胞系(A2780cis和A2780)对铂物种的相对摄取。所获得的结果揭示了这种分析策略的潜力，以区分对药物不同敏感的不同细胞系，这可能具有很高的医学价值。
One of the main limitations to the Pt-therapy in cancer is the development of associated drug resistance that can be associated with a significant reduction of the intracellular platinum concentration. Thus, intracellular Pt concentration could be considered as a biomarker of cisplatin resistance. In this work, an alternative method to address intracellular Pt concentration in individual cells is explored to permit the evaluation of different cell models and alternative therapies in a relatively fast way. For this aim, total Pt analysis in single cells has been implemented using a total consumption nebulizer coupled to inductively coupled plasma mass spectrometric detection (ICP-MS). The efficiency of the proposed device has been evaluated in combination with flow cytometry and turned out to be around 25% (cells entering the ICP-MS from the cells in suspension). Quantitative uptake studies of a nontoxic Tb-containing compound by individual cells were conducted and the results compared to those obtained by bulk analysis of the same cells. Both sets of data were statistically comparable. Thus, final application of the developed methodology to the comparative uptake of Pt-species in cisplatin resistant and sensitive cell lines (A2780cis and A2780) was conducted. The results obtained revealed the potential of this analytical strategy to differentiate between different cell lines of different sensitivity to the drug which might be of high medical interest.