Mass cytometric study on the heterogeneity in cellular association and cytotoxicity of silver nanoparticles in primary human immune cells,Environmental Science: Nano

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Mass cytometric study on the heterogeneity in cellular association and cytotoxicity of silver nanoparticles in primary human immune cells
Environmental Science: Nano ( IF 5.8 ) Pub Date : 2020-02-18 , DOI: 10.1039/c9en01104h
My Kieu Ha _{1,

2,

3,

4,

5} , Jang-Sik Choi _{1,

2,

3,

4,

6} , Sook Jin Kwon _{1,

2,

3,

4,

6} , Jaewoo Song _{4,

7,

8,

9,

10} , Yangsoon Lee _{2,

3,

4,

7,

8} , Young-Eun Kim _{2,

3,

4,

7,

8} , Tae Hyun Yoon _{1,

2,

3,

4,

5}

Affiliation

In recent years, there have been remarkable efforts to examine and understand the adverse effects of nanoparticles (NPs) on the environment and human health, not only qualitatively but also quantitatively. Mass cytometry has been developed for high-dimensional single-cell analyses and used to quantify the cellular association of inorganic NPs. Here, we have applied this novel technique to investigate the heterogeneity in cellular association and cytotoxicity of polyvinylpyrrolidone-coated silver nanoparticles with diameters of 10 nm and 20 nm in primary human immune cells. Our results revealed the cell-type-dependent heterogeneity in which AgNPs showed higher affinity to phagocytic cells like monocytes and dendritic cells than to other immune cell types. Upon exposure to AgNPs, these cells exhibited complex pro-inflammatory and pro-apoptotic responses, such as IκBα degradation, STAT1 phosphorylation and caspase-7 activation. Quantitative analyses of the single-cell dose–response relationship between the cellular AgNP association and signalling activities further revealed heterogeneity even within a monocyte population. The majority of cells belonged to the ‘low affinity’ subset, which showed a positive AgNP dose–cisplatin uptake (i.e. viability loss) correlation, as opposed to the remaining cells which belonged to the ‘high affinity’ subset and had an insignificant relationship between the cell-associated AgNP amount and cisplatin uptake/viability loss level. These subsets were distinctly responsive to the cellular AgNP content, as they showed different levels of signalling proteins such as IκBα, STAT1 and caspase-7. Our study can be helpful for further understanding the heterogeneous nature of cell–NP interactions and development of dose–response models at the single-cell level for various NPs, which will provide key information for the safe use of nanomaterials in biomedical applications.

中文翻译：

大量细胞学研究原代人免疫细胞中银纳米颗粒的细胞缔合异质性和细胞毒性

近年来，人们进行了巨大的努力，不仅从质上而且从数量上研究和理解了纳米颗粒（NPs）对环境和人类健康的不利影响。已经开发了用于高维单细胞分析的大规模细胞计数法，并用于量化无机NP的细胞缔合。在这里，我们已经应用了这项新颖的技术来研究原代人免疫细胞中直径10 nm和20 nm的聚乙烯吡咯烷酮包覆的银纳米颗粒在细胞缔合中的异质性和细胞毒性。我们的研究结果揭示了AgNPs对吞噬细胞（如单核细胞和树突状细胞）的亲和力高于对其他免疫细胞类型的依赖于细胞类型的异质性。暴露于AgNPs后，这些细胞表现出复杂的促炎和促凋亡反应，例如IκBα降解，STAT1磷酸化和caspase-7活化。定量分析细胞中AgNP缔合与信号传导活性之间的单细胞剂量-反应关系，甚至揭示了单核细胞群中的异质性。大多数细胞属于“低亲和力”子集，其显示出正的AgNP剂量–顺铂摄取（（即生存力丧失）相关性，与属于“高亲和力”子集且与细胞相关的AgNP量与顺铂摄取/生存力丧失水平之间的关系不明显的其余细胞相反。这些子集对细胞中的AgNP含量有明显的反应，因为它们显示出不同水平的信号传导蛋白，例如IκBα，STAT1和caspase-7。我们的研究有助于进一步了解细胞与NP相互作用的异质性，并为各种NP在单细胞水平上建立剂量反应模型，这将为纳米材料在生物医学应用中的安全使用提供关键信息。

更新日期：2020-02-18

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