High-Throughput Single Cell Analysis Reveals the Heterogeneity of QDots-Induced Response in Macrophages,Environmental Science & Technology Letters

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High-Throughput Single Cell Analysis Reveals the Heterogeneity of QDots-Induced Response in Macrophages
Environmental Science & Technology Letters ( IF 8.9 ) Pub Date : 2020-04-14 , DOI: 10.1021/acs.estlett.0c00278
Yuanyuan Wang _{1,

2} , Ligang Hu _{2,

3} , Tian Xia ₄ , Xinglei Yao ₁ , Yongguang Yin _{1,

2} , Fengbang Wang _{1,

2} , Maoyong Song _{1,

2} , Guibin Jiang _{2,

3}

Affiliation

The ability to assess the responses of cells exposed to nanoparticles at the single cell level will lead to mechanistic understanding of their toxicity and safety. Here, we demonstrated the heterogeneity of cell uptake and cellular responses in a QDots-exposed macrophage using a high-content screening (HCS) analysis. The dynamic uptake and intracellular location of QDots were characterized by HCS due to its fluorescence. We further verified the association between fluorescence intensity and mass concentration of intracellular QDots using combined methods. The heterogeneity of multiple cell responses, including apoptosis, autophagy, calcium influx, mitochondria membrane potential, nucleus size, and reactive oxygen species generation, was analyzed for fingerprinting of the cytotoxicity of QDots at the single cell level. On the basis of the heterogeneity and the established dose–response relationship, we illustrated that ROS generation was the most sensitive parameter to intracellular QDots. This study makes an important methodological contribution to nanotoxicology with much higher throughput and accuracy at the single cell level.

中文翻译：

高通量单细胞分析揭示了巨噬细胞中QDots诱导反应的异质性。

在单个细胞水平上评估暴露于纳米颗粒的细胞反应的能力将导致对其毒性和安全性的机械理解。在这里，我们展示了使用高内涵筛选（HCS）分析在QDots暴露的巨噬细胞中细胞摄取和细胞应答的异质性。由于其荧光，HCS表征了QDots的动态摄取和细胞内位置。我们进一步验证了荧光强度和细胞内QDots质量浓度之间的关联，使用组合方法。分析了多种细胞反应的异质性，包括细胞凋亡，自噬，钙内流，线粒体膜电位，细胞核大小和活性氧物种生成，以分析单细胞水平QDots的细胞毒性。基于异质性和已建立的剂量反应关系，我们说明了ROS的产生是对细胞内QDots最敏感的参数。这项研究对纳米毒理学做出了重要的方法学贡献，在单细胞水平上具有更高的通量和准确性。

更新日期：2020-04-14

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