MRC/University of Edinburgh, Centre for Inflammation Research, Queen's Medical Research Institute,47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom.
Toxicol Sci. 2012 Aug;128(2):461-70. doi: 10.1093/toxsci/kfs171. Epub 2012 May 12.
Suspicion has been raised that high aspect ratio nanoparticles or nanofibers might possess asbestos-like pathogenicity. The pleural space is a specific target for disease in individuals exposed to asbestos and by implication of nanofibers. Pleural effects of fibers depends on fiber length, but the key threshold length beyond which adverse effects occur has never been identified till now because all asbestos and vitreous fiber samples are heterogeneously distributed in their length. Nanotechnology advantageously allows for highly defined length distribution of synthetically engineered fibers that enable for in-depth investigation of this threshold length. We utilized the ability to prepare silver nanofibers of five defined length classes to demonstrate a threshold fiber length for acute pleural inflammation. Nickel nanofibers and carbon nanotubes were then used to strengthen the relationship between fiber length and pleural inflammation. A method of intrapleural injection of nanofibers in female C57Bl/6 strain mice was used to deliver the fiber dose, and we then assessed the acute pleural inflammatory response. Chest wall sections were examined by light and scanning electron microscopy to identify areas of lesion; furthermore, cell-nanowires interaction on the mesothelial surface of the parietal pleura in vivo was investigated. Our results showed a clear threshold effect, demonstrating that fibers beyond 4 µm in length are pathogenic to the pleura. The identification of the threshold length for nanofiber-induced pathogenicity in the pleura has important implications for understanding the structure-toxicity relationship for asbestos-induced mesothelioma and consequent risk assessment with the aim to contribute to the engineering of synthetic nanofibers by the adoption of a benign-by-design approach.
人们怀疑高长径比纳米粒子或纳米纤维可能具有类似石棉的致病性。胸膜是个体暴露于石棉和纳米纤维后疾病的特定靶标。纤维的胸膜效应取决于纤维长度，但迄今为止，尚未确定发生不良影响的关键阈值长度，因为所有石棉和玻璃纤维样品的长度都呈异质分布。纳米技术有利地允许合成工程纤维具有高度定义的长度分布，从而能够深入研究该阈值长度。我们利用制备具有五个定义长度类别的银纳米纤维的能力来证明急性胸膜炎症的纤维阈值长度。然后，使用镍纳米纤维和碳纳米管来加强纤维长度与胸膜炎症之间的关系。使用在雌性 C57Bl/6 品系小鼠中进行胸膜内注射纳米纤维的方法来输送纤维剂量，然后我们评估了急性胸膜炎症反应。用光镜和扫描电子显微镜检查胸壁切片以确定病变区域；此外，还研究了体内壁层胸膜上皮细胞-纳米线相互作用。我们的结果显示出明显的阈值效应，表明长度超过 4 µm 的纤维对胸膜具有致病性。确定纳米纤维诱导的胸膜致病性的阈值长度对于理解石棉诱导的间皮瘤的结构-毒性关系以及随后的风险评估具有重要意义，目的是通过采用良性设计方法来促进合成纳米纤维的工程设计。
