Abstract: With the increasing production and application of engineered amorphous silica nanoparticles (aSiNPs), people have more opportunities to be exposed to aSiNPs. However, the knowledge of its adverse health effects and related mechanisms is still limited, compared with the well-studied crystalline micron-sized silica. Since small differences in the physical–chemical properties of nanoparticles could cause significant differences in the toxic effect, it is important to distinguish how these variations influence the outcoming toxicity. Notably, particle size, as one of the essential characterizations of aSiNPs, is relevant to its biological activities. Thus, the aim of this systematic review was to summarize the relationship between the particle size of aSiNPs and its adverse biological effects. In order to avoid the influence of complicated in vivo experimental conditions on the toxic outcome, only in vitro toxicity studies which reported on the cytotoxic effect of different sizes aSiNPs were included. After the systematic literature retrieval, selection, and quality assessment process, 76 eligible scientific papers were finally included in this review. There were 76% of the studies that concluded a size-dependent cytotoxicity of aSiNPs, in which smaller-sized aSiNPs possessed greater toxicity. However, this trend could be modified by certain influence factors, such as the synthetic method of aSiNPs, particle aggregation state in cell culture medium, toxicity endpoint detection method, and some other experimental conditions. The effects of these influence factors on the size-dependent cytotoxicity of aSiNPs were also discussed in detail in the present review.

Keywords: silica nanoparticles, particle size, cytotoxicity, cell death, nanotoxicology, influence factors


中文翻译：

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非晶硅纳米粒子的尺寸依赖性细胞毒性：体外研究的系统综述。

摘要：随着工程无定形二氧化硅纳米颗粒（aSiNPs）的生产和应用的增加，人们有更多机会接触aSiNPs。但是，与经过深入研究的结晶微米级二氧化硅相比，其不良健康影响和相关机理的知识仍然有限。由于纳米粒子的物理化学性质的微小差异可能会导致毒性作用的显着差异，因此重要的是要区分这些差异如何影响即将产生的毒性。值得注意的是，作为aSiNPs的基本特征之一，粒径与其生物学活性有关。因此，本系统综述的目的是总结aSiNPs的粒径与其不良生物学效应之间的关系。为了避免复杂的体内实验条件对毒性结果的影响，仅包括体外毒性研究，该研究报道了不同大小的aSiNPs的细胞毒性作用。经过系统的文献检索，选择和质量评估过程，最终收录了76篇合格的科学论文。有76％的研究得出了aSiNPs的大小依赖性细胞毒性的结论，其中较小尺寸的aSiNPs具有更大的毒性。但是，这种趋势可能会受到某些影响因素的影响，例如aSiNPs的合成方法，细胞培养基中颗粒的聚集状态，毒性终点检测方法以及其他一些实验条件。

关键词：二氧化硅纳米粒子粒径细胞毒性细胞死亡纳米毒理学影响因素