Although both dissolved Zn²⁺ and nano-ZnO (nZnO) contribute to ZnO toxicity, their specific roles as well as intracellular transformation and transport are inconclusive. In this study, for the first time, nZnO particles with different physicochemical properties were synthesized to provide different dissolution potentials and subcellular behaviors. We then examined the inter-relationships between extra/intracellularly dissolved Zn²⁺ and subcellular stress responses in zebrafish cells. A novel Zn²⁺-initiated aggregation-induced emission fluorogen was used to quantify the dissolution of nZnO and trace the intracellular transport of labile Zn²⁺. Over a 24 h exposure to nZnO, the extracellular dissolution potential determined the intracellular Zn²⁺ level. However, the low extracellular dissolution potential of nZnO stimulated lysosomal accumulation and reactive oxygen species (ROS) production. We showed that the lysosome was the first cellular system to process the internalized Zn, which resulted in two peaks of ROS production caused by activated lysosomes and then by mitochondrial burdens. The dissolution ability of nZnO could not perfectly explain the cellular stress, whereas both the contents and properties of nZnO determined more. Our study demonstrates a unique interplay between Zn²⁺ and nZnO, which subsequently determined the dynamic cellular stress caused by nZnO.

中文翻译：

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Zn2+ 和 nZnO 之间独特的相互作用决定了斑马鱼细胞的动态细胞应激

尽管溶解的 Zn ²⁺和纳米 ZnO (nZnO) 都会导致 ZnO 毒性，但它们的具体作用以及细胞内转化和转运尚无定论。在这项研究中，首次合成了具有不同理化性质的 nZnO 颗粒，以提供不同的溶解电位和亚细胞行为。然后我们检查了细胞外/细胞内溶解的 Zn ²⁺与斑马鱼细胞中亚细胞应激反应之间的相互关系。使用新型 Zn ²⁺引发的聚集诱导发射荧光来量化 nZnO 的溶解并追踪不稳定的 Zn ²⁺的细胞内转运. 在接触 nZnO 24 小时后，细胞外溶解电位决定了细胞内 Zn ²⁺水平。然而，nZnO 的低细胞外溶解潜力刺激了溶酶体的积累和活性氧 (ROS) 的产生。我们发现溶酶体是第一个处理内化锌的细胞系统，这导致了由活化的溶酶体和线粒体负荷引起的两个 ROS 产生峰值。nZnO 的溶解能力不能很好地解释细胞应力，而 nZnO 的含量和性质决定了更多。我们的研究表明 Zn ²⁺和 nZnO之间存在独特的相互作用，随后确定了由 nZnO 引起的动态细胞应力。