Amorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles. Consistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content. Surface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.

中文翻译：

---

设计更安全的火焰喷涂二氧化硅纳米颗粒：硅烷醇含量对ROS生成，表面活性和细胞毒性的作用。

非晶态二氧化硅纳米粒子（SiO2 NPs）被认为是相对良性的纳米材料，然而，近年来，有关体外和体内毒性的几篇报道对这种广泛持有的观点提出了质疑。表面化学，更具体地说是表面硅烷醇含量，已被确定为SiO2 NPs的重要毒性调节剂。在这里，已确定了SiO2 NPs上硅烷醇含量，自由基生成和毒性之间的定量关系，目的是合成设计更安全的气相二氧化硅纳米颗粒。在巨噬细胞RAW264.7中，总硅醇含量，细胞膜损伤和细胞活力之间存在一致且统计上显着的趋势，但与细胞内活性氧（ROS）无关。总硅烷醇含量较低的SiO2 NPs表现出较大的不利细胞效应。SAEC上皮细胞系未显示任何纳米颗粒的任何毒性迹象。这些纳米颗粒的自由基产生和表面反应性也受到燃烧温度和总硅烷醇含量的影响。表面硅烷醇含量在细胞毒性和表面反应性中起着重要作用，尽管它可能不是影响气相二氧化硅NP毒性的唯一因素。结果表明，SiO2 NPs的合成条件会影响自由基的类型和数量，氧化应激，纳米颗粒与它们所接触的生物环境的相互作用，并确定毒性的具体机制。