In the last 30 years the research about zinc oxide nanoparticles (ZnO NPs) and their related toxicity has shown a boom. ZnO NPs show cytotoxicity for both prokaryotic and eukaryotic cells and many studies demonstrated their selective toxicity towards cancer cells. However, with the increasing number of publications, it is observed an increase in the discrepancies obtained between the various results. Soon the scientific community understood that the ZnO NC toxicity behaviour is affected by many factors, related not only to the ZnO NPs themselves, but also to the experimental conditions used. Many recent reviews discussed these parameters by reporting experimental evidence and tried to assess the general statements about the ZnO NP cytotoxicity. This information is extremely useful for the evaluation of which type of ZnO NPs is more or less suitable for a specific study or application. However, despite that, a deep comprehension of the ZnO NP behaviour in relation to the different experimental conditions is still lacking. Actually, a full understanding of the reasons behind the NP behaviour is essential to better assess their biological activity and in particular their therapeutic application, avoiding undesired effects both in the experimental and clinical contexts. This tutorial review aims to be an experimental and practical guide for scientists that faced with the use of ZnO NPs for biomedical applications and, in particular, for their therapeutic purposes. The driving idea is to not simply summarize the results reported in the literature, but to provide instruments for a deep comprehension of the mechanisms affecting the ZnO NP cytotoxicity and behavior. This review also aims to point out the critical experimental parameters to be considered when working with these NPs, as well as the main related risks and limitations that scientists have to face.

中文翻译：

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影响氧化锌纳米颗粒细胞毒性行为的参数的研究：教程回顾

在过去的 30 年中，关于氧化锌纳米粒子 (ZnO NPs) 及其相关毒性的研究呈现出蓬勃发展的态势。ZnO NPs 对原核细胞和真核细胞均显示出细胞毒性，许多研究表明它们对癌细胞具有选择性毒性。但是，随着出版物数量的增加，可以观察到各种结果之间的差异越来越大。很快，科学界就了解到 ZnO NC 的毒性行为受许多因素的影响，不仅与 ZnO NPs 本身有关，还与所使用的实验条件有关。许多最近的评论通过报告实验证据讨论了这些参数，并试图评估关于 ZnO NP 细胞毒性的一般陈述。此信息对于评估哪种类型的 ZnO NP 或多或少适合特定研究或应用非常有用。然而，尽管如此，仍然缺乏对与不同实验条件相关的 ZnO NP 行为的深入理解。实际上，充分了解 NP 行为背后的原因对于更好地评估其生物活性，尤其是其治疗应用，避免在实验和临床环境中产生不良影响至关重要。本教程综述旨在为面临将 ZnO NP 用于生物医学应用，特别是用于治疗目的的科学家提供实验和实用指南。驱动思想不是简单地总结文献中报道的结果，但为深入理解影响 ZnO NP 细胞毒性和行为的机制提供工具。本综述还旨在指出在使用这些 NP 时要考虑的关键实验参数，以及科学家必须面对的主要相关风险和限制。