High throughput toxicity screening and intracellular detection of nanomaterials.
High throughput toxicity screening and intracellular detection of nanomaterials.
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DOI：
10.1002/wnan.1413
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发表时间：
2017-01
影响因子：
8.6
通讯作者：
Dusinska, Maria
中科院分区：
文献类型：
--
作者：
Collins, Andrew R.;Annangi, Balasubramanyam;Rubio, Laura;Marcos, Ricard;Dorn, Marco;Merker, Carolin;Estrela-Lopis, Irina;Cimpan, Mihaela Roxana;Ibrahim, Mohamed;Cimpan, Emil;Ostermann, Melanie;Sauter, Alexander;El Yamani, Naouale;Shaposhnikov, Sergey;Chevillard, Sylvie;Paget, Vincent;Grall, Romain;Delic, Jozo;Goni-de-Cerio, Felipe;Suarez-Merino, Blanca;Fessard, Valerie;Hogeveen, Kevin N.;Fjellsbo, Lise Maria;Pran, Elise Runden;Brzicova, Tana;Topinka, Jan;Silva, Maria Joao;Leite, P. E.;Ribeiro, A. R.;Granjeiro, J. M.;Grafstrom, Roland;Prina-Mello, Adriele;Dusinska, Maria
随着越来越多的纳米材料（NM），有一个快速和可靠的方法来测试NM的安全性，最好使用体外方法，以避免与动物研究的伦理困境的巨大需求。基于分组和交叉阅读方法，需要数据来制定用于NM风险评估的智能测试策略。采用高通量筛选（HTS）和高含量分析（HCA）进行NM毒性测试，可以在不同浓度和不同类型的细胞上测试多种材料，减少实验间差异的影响，并大幅节省时间和成本。HTS/HCA方法有助于对NM-细胞相互作用的关键生物学指标进行分类。考虑到与体内结果的相关性，需要对体外HTS试验进行验证。需要HTS/HCA方法来评估剂量和时间依赖性毒性，从而预测体内不良反应。正在对几种HTS/HCA方法进行验证，并将其应用于FP 7项目NANoREG中的NM检测，包括NM摄取的无标记细胞筛选、HCA、高通量流式细胞术、基于阻抗的监测、分泌产物的多重分析和遗传毒性方法-即高通量彗星试验、高通量体外微核试验和γ H2 AX试验。HTS/HCA用于NM测试存在若干技术挑战，因为在测试之前，毒性筛选需要与暴露介质中NM的表征相结合; NM对HTS/HCA技术的可能干扰是另一个问题。讨论了HTS/HCA方法在NM安全方面的优势和挑战。WIREs Nanomed Nanobiotechnol 2017，9：e1413. doi：10.1002/wnan.1413有关本文的更多资源，请访问WIREs网站。
With the growing numbers of nanomaterials (NMs), there is a great demand for rapid and reliable ways of testing NM safety—preferably using in vitro approaches, to avoid the ethical dilemmas associated with animal research. Data are needed for developing intelligent testing strategies for risk assessment of NMs, based on grouping and read‐across approaches. The adoption of high throughput screening (HTS) and high content analysis (HCA) for NM toxicity testing allows the testing of numerous materials at different concentrations and on different types of cells, reduces the effect of inter‐experimental variation, and makes substantial savings in time and cost. HTS/HCA approaches facilitate the classification of key biological indicators of NM‐cell interactions. Validation of in vitro HTS tests is required, taking account of relevance to in vivo results. HTS/HCA approaches are needed to assess dose‐ and time‐dependent toxicity, allowing prediction of in vivo adverse effects. Several HTS/HCA methods are being validated and applied for NM testing in the FP7 project NANoREG, including Label‐free cellular screening of NM uptake, HCA, High throughput flow cytometry, Impedance‐based monitoring, Multiplex analysis of secreted products, and genotoxicity methods—namely High throughput comet assay, High throughput in vitro micronucleus assay, and γH2AX assay. There are several technical challenges with HTS/HCA for NM testing, as toxicity screening needs to be coupled with characterization of NMs in exposure medium prior to the test; possible interference of NMs with HTS/HCA techniques is another concern. Advantages and challenges of HTS/HCA approaches in NM safety are discussed. WIREs Nanomed Nanobiotechnol 2017, 9:e1413. doi: 10.1002/wnan.1413 For further resources related to this article, please visit the WIREs website.
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