The puzzling issue of silica toxicity: are silanols bridging the gaps between surface states and pathogenicity?
The puzzling issue of silica toxicity: are silanols bridging the gaps between surface states and pathogenicity?
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DOI：
10.1186/s12989-019-0315-3
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发表时间：
2019-08-16
影响因子：
10
通讯作者：
Turci, Francesco
中科院分区：
文献类型：
--
作者：
Pavan, Cristina;Delle Piane, Massimo;Turci, Francesco
二氧化硅仍然代表着从地质学到物理学、化学、细胞生物学和粒子毒理学等各个科学领域的基础和应用研究的一个有趣主题。二氧化硅的致病活性是可变的，取决于颗粒的物理化学特征。在过去的50年中，结晶度和产生自由基的能力已被认为是二氧化硅毒性的相关特征。“表面”在二氧化硅毒性中也起着重要作用，但这个术语通常以非常笼统的方式使用，而没有定义表面的哪些特性实际上是驱动毒性的。化学特性（例如，硅醇和硅氧烷）和二氧化硅表面的构型可引发毒性反应，这仍然不完全清楚。表面化学、细胞生物学和毒理学的最新进展为我们更好地理解二氧化硅颗粒不良反应的分子机制提供了新的途径。新的物理化学方法可以精细地表征和量化二氧化硅颗粒表面的硅烷醇。先进的计算建模和原子力显微镜提供了独特的机会，探索二氧化硅表面和膜模型或细胞之间的密切相互作用。近年来，跨学科的研究，使用这些工具，已经建立了越来越多的证据表明，表面硅烷醇是二氧化硅颗粒和生物分子，膜，细胞系统或动物模型之间相互作用的关键决定因素。同样清楚的是，硅烷醇的构型以及最终的生物反应可能受到晶体结构内的杂质或覆盖颗粒表面的涂层的影响。免疫系统和肺上皮细胞中结晶和无定形二氧化硅颗粒的新分子靶点的发现代表了新的可能毒性途径。已经鉴定了检测二氧化硅颗粒表面的特定特征的细胞识别系统。结论跨学科研究将表面化学与毒理学联系起来，正逐步解决二氧化硅毒性可变这一令人困惑的问题。进一步的跨学科研究正在进行中，以阐明二氧化硅致病性的内在机制，以可能减轻或减少表面反应性。
Background Silica continues to represent an intriguing topic of fundamental and applied research across various scientific fields, from geology to physics, chemistry, cell biology, and particle toxicology. The pathogenic activity of silica is variable, depending on the physico-chemical features of the particles. In the last 50 years, crystallinity and capacity to generate free radicals have been recognized as relevant features for silica toxicity. The 'surface' also plays an important role in silica toxicity, but this term has often been used in a very general way, without defining which properties of the surface are actually driving toxicity. How the chemical features (e.g., silanols and siloxanes) and configuration of the silica surface can trigger toxic responses remains incompletely understood. Main body Recent developments in surface chemistry, cell biology and toxicology provide new avenues to improve our understanding of the molecular mechanisms of the adverse responses to silica particles. New physico-chemical methods can finely characterize and quantify silanols at the surface of silica particles. Advanced computational modelling and atomic force microscopy offer unique opportunities to explore the intimate interactions between silica surface and membrane models or cells. In recent years, interdisciplinary research, using these tools, has built increasing evidence that surface silanols are critical determinants of the interaction between silica particles and biomolecules, membranes, cell systems, or animal models. It also has become clear that silanol configuration, and eventually biological responses, can be affected by impurities within the crystal structure, or coatings covering the particle surface. The discovery of new molecular targets of crystalline as well as amorphous silica particles in the immune system and in epithelial lung cells represents new possible toxicity pathways. Cellular recognition systems that detect specific features of the surface of silica particles have been identified. Conclusions Interdisciplinary research bridging surface chemistry to toxicology is progressively solving the puzzling issue of the variable toxicity of silica. Further interdisciplinary research is ongoing to elucidate the intimate mechanisms of silica pathogenicity, to possibly mitigate or reduce surface reactivity.