Gioria Sabrina, Lobo Vicente Joana, Barboro Paola, La Spina Rita, Tomasi Giorgio, Urbán Patricia, Kinsner-Ovaskainen Agnieszka, François Rossi, Chassaigne Hubert
a European Commission, Joint Research Centre, Institute for Health and Consumer Protection , Ispra , Italy and.
b IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro , Genova , Italy.
Nanotoxicology. 2016 Aug;10(6):736-48. doi: 10.3109/17435390.2015.1121412. Epub 2016 Feb 10.
Omics technologies, such as proteomics or metabolomics, have to date been applied in the field of nanomaterial safety assessment to a limited extent. To address this dearth, we developed an integrated approach combining the two techniques to study the effects of two sizes, 5 and 30 nm, of gold nanoparticles (AuNPs) in Caco-2 cells. We observed differences in cells exposed for 72 h to each size of AuNPs: 61 responsive (up/down-regulated) proteins were identified and 35 metabolites in the cell extract were tentatively annotated. Several altered biological pathways were highlighted by integrating the obtained multi-omics data with bioinformatic tools. This provided a unique set of molecular information on the effects of nanomaterials at cellular level. This information was supported by complementary data obtained by immunochemistry, microscopic analysis, and multiplexed assays. A part from increasing our knowledge on how the cellular processes and pathways are affected by nanomaterials (NMs), these findings could be used to identify specific biomarkers of toxicity or to support the safe-by-design concept in the development of new nanomedicines.
蛋白质组学或代谢组学等组学技术,迄今为止在纳米材料安全性评估领域的应用程度有限。为解决这一不足,我们开发了一种综合方法,将这两种技术结合起来,以研究5纳米和30纳米两种尺寸的金纳米颗粒(AuNP)对Caco-2细胞的影响。我们观察到,暴露于每种尺寸AuNP 72小时的细胞存在差异:鉴定出61种有反应(上调/下调)的蛋白质,并初步注释了细胞提取物中的35种代谢物。通过将获得的多组学数据与生物信息学工具相结合,突出了几个改变的生物途径。这提供了关于纳米材料在细胞水平上作用的独特分子信息集。这些信息得到了免疫化学、显微镜分析和多重检测获得的补充数据的支持。除了增加我们对细胞过程和途径如何受到纳米材料(NM)影响的了解之外,这些发现还可用于识别特定的毒性生物标志物或支持新纳米药物开发中的设计安全性概念。