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Effects of size and surface of zinc oxide and aluminum-doped zinc oxide nanoparticles on cell viability inferred by proteomic analyses

机译:氧化锌和铝掺杂的氧化锌纳米粒子的大小和表面对蛋白质组学分析推断细胞活力的影响

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摘要

Although the health effects of zinc oxide nanoparticles (ZnONPs) on the respiratory system have been reported, the fate, potential toxicity, and mechanisms in biological cells of these particles, as related to particle size and surface characteristics, have not been well elucidated. To determine the physicochemical properties of ZnONPs that govern cytotoxicity, we investigated the effects of size, electronic properties, zinc concentration, and pH on cell viability using human alveolar-basal epithelial A549 cells as a model. We observed that a 2-hour or longer exposure to ZnONPs induced changes in cell viability. The alteration in cell viability was associated with the zeta potentials and pH values of the ZnONPs. Proteomic profiling of A549 exposed to ZnONPs for 2 and 4 hours was used to determine the biological mechanisms of ZnONP toxicity. p53-pathway activation was the core mechanism regulating cell viability in response to particle size. Activation of the Wnt and TGFβ signaling pathways was also important in the cellular response to ZnONPs of different sizes. The cadherin and Wnt signaling pathways were important cellular mechanisms triggered by surface differences. These results suggested that the size and surface characteristics of ZnONPs might play an important role in their observed cytotoxicity. This approach facilitates the design of more comprehensive systems for the evaluation of nanoparticles.
机译:尽管已经报道了氧化锌纳米颗粒(ZnONPs)对呼吸系统的健康影响,但尚未很好地阐明这些颗粒的命运,潜在毒性以及这些颗粒在生物细胞中的机制,与颗粒大小和表面特性有关。为了确定控制细胞毒性的ZnONP的理化特性,我们使用人肺泡基底上皮A549细胞作为模型,研究了大小,电子特性,锌浓度和pH对细胞活力的影响。我们观察到2个小时或更长时间的ZnONP暴露会诱导细胞活力的变化。细胞活力的改变与ZnONP的ζ电位和pH值有关。暴露于ZnONP 2小时和4小时的A549的蛋白质组分析用于确定ZnONP毒性的生物学机制。 p53途径激活是调节细胞活力以响应粒径的核心机制。 Wnt和TGFβ信号通路的激活在细胞对不同大小ZnONP的反应中也很重要。钙粘蛋白和Wnt信号通路是由表面差异触发的重要细胞机制。这些结果表明,ZnONP的大小和表面特征可能在其观察到的细胞毒性中起重要作用。这种方法有助于设计用于评估纳米颗粒的更全面的系统。

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