Toxicity screenings of nanomaterials: challenges due to interference with assay processes and components of classic in vitro tests
Toxicity screenings of nanomaterials: challenges due to interference with assay processes and components of classic in vitro tests
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DOI：
10.3109/17435390.2013.829590
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发表时间：
2015-05-01
期刊：
影响因子：
5
通讯作者：
Boland, Sonja
中科院分区：
文献类型：
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作者：
Guadagnini, Rina;Kenzaoui, Blanka Halamoda;Boland, Sonja
鉴于纳米粒子（NP）的多样性，需要制定筛选策略来评估其毒性。在欧盟资助的 FP7 NanoTEST 项目中，一组医学相关的 NP 已被用来开发用于医学诊断的 NP 的替代测试策略。由于传统的毒性测试不一定能像可溶性化学品和药物那样直接应用于纳米颗粒，因此我们确定了纳米颗粒对每个测定过程和成分的干扰程度。在本研究中，我们全面表征了本项目中使用的纳米颗粒悬浮液组（聚乳酸-乙醇酸）聚环氧乙烷 [PLGA-PEO]、TiO2、SiO2 以及未包覆和油酸包覆的 Fe3O4），并表明许多 NP 特性（成分、尺寸、包覆和团聚）会干扰一系列体外细胞毒性测定（WST-1、MTT、乳酸脱氢酶、中性）。红、碘化丙啶、H-3-胸苷掺入和细胞计数）、促炎反应评估（GM-CSF、IL-6 和 IL-8 的 ELISA）和氧化应激检测（monoBromoBimane、二氯荧光素和 NO 测定）。干扰是检测特异性的以及 NP 特异性的。我们提出如何集成和避免干扰测试系统，作为生物医学纳米粒子筛选策略的第一步。
Given the multiplicity of nanoparticles (NPs), there is a requirement to develop screening strategies to evaluate their toxicity. Within the EU-funded FP7 NanoTEST project, a panel of medically relevant NPs has been used to develop alternative testing strategies of NPs used in medical diagnostics. As conventional toxicity tests cannot necessarily be directly applied to NPs in the same manner as for soluble chemicals and drugs, we determined the extent of interference of NPs with each assay process and components. In this study, we fully characterized the panel of NP suspensions used in this project (poly(lactic-co-glycolic acid)polyethylene oxide [PLGA-PEO], TiO2, SiO2, and uncoated and oleic-acid coated Fe3O4) and showed that many NP characteristics (composition, size, coatings, and agglomeration) interfere with a range of in vitro cytotoxicity assays (WST-1, MTT, lactate dehydrogenase, neutral red, propidium iodide, H-3-thymidine incorporation, and cell counting), pro-inflammatory response evaluation (ELISA for GM-CSF, IL-6, and IL-8), and oxidative stress detection (monoBromoBimane, dichlorofluorescein, and NO assays). Interferences were assay specific as well as NP specific. We propose how to integrate and avoid interference with testing systems as a first step of a screening strategy for biomedical NPs.