CuO nanoparticles (NPs) show promising applications in biosensors, waste treatment, and energy materials, but the growing manufacture of CuO NPs also leads to the concerns for their potential environmental and health risks. However, the cellular fates of CuO NPs such as Cu ion dissolution, transformation, and efflux remain largely speculative. In the present study, we for the first time combined the gold-core labeling and Cu ion bioimaging technologies to reveal the intracellular fates of CuO NPs in different cells following cellular internalization of NPs. We demonstrated that the dissolution rate of CuO NPs depended on the cell type. Following CuO dissolution, limited transformation of Cu(II) to Cu(I) occurred within the cellular microenvironment. Instead, Cu(II) was rapidly eliminated from the cells, and such rapid efflux in different cells was highly dependent on the GSH-mediated pathway and lysosome exocytosis. The labile Cu(I) level in the two cancerous cell lines was immediately regulated upon Cu exposure, which explained their tolerance to Au@CuO NPs. Overall, our study demonstrated a very rapid turnover of Cu in the cells following CuO internalization, which subsequently determined the cellular toxicity of CuO. The results will have important implications for assessing the health risk of CuO NPs.

中文翻译：

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CuO纳米颗粒的细胞类型依赖性溶解和细胞内化后Cu离子的流出

CuO 纳米颗粒 (NPs) 在生物传感器、废物处理和能源材料中显示出有前景的应用，但 CuO NPs 的日益增长的制造也导致了对其潜在环境和健康风险的担忧。然而，CuO NPs 的细胞命运，如 Cu 离子溶解、转化和流出，在很大程度上仍然是推测性的。在本研究中，我们首次结合金核标记和铜离子生物成像技术，揭示了 NPs 细胞内化后 CuO NPs 在不同细胞中的细胞内命运。我们证明了 CuO NPs 的溶解速率取决于细胞类型。在 CuO 溶解后，Cu(II) 向 Cu(I) 的有限转化发生在细胞微环境中。相反，Cu(II) 迅速从细胞中消除，并且这种在不同细胞中的快速流出高度依赖于 GSH 介导的途径和溶酶体胞吐作用。两种癌细胞系中不稳定的 Cu(I) 水平在 Cu 暴露后立即受到调节，这解释了它们对 Au@CuO NPs 的耐受性。总体而言，我们的研究证明了 CuO 内化后细胞中 Cu 的非常快速的转换，这随后确定了 CuO 的细胞毒性。该结果将对评估 CuO NPs 的健康风险具有重要意义。随后确定了CuO的细胞毒性。该结果将对评估 CuO NPs 的健康风险具有重要意义。随后确定了CuO的细胞毒性。该结果将对评估 CuO NPs 的健康风险具有重要意义。