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结合细胞毒性评估和非洲爪蟾表型异常分析作为纳米材料安全性的预测指标

Combining Cytotoxicity Assessment and Xenopus laevis Phenotypic Abnormality Assay as a Predictor of Nanomaterial Safety.

作者信息

Al-Yousuf Karamallah, Webster Carl A, Wheeler Grant N, Bombelli Francesca Baldelli, Sherwood Victoria

机构信息

Skin Tumour Laboratory, Jacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, United Kingdom.

School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, United Kingdom.

出版信息

Curr Protoc Toxicol. 2017 Aug 4;73:20.13.1-20.13.33. doi: 10.1002/cptx.25.

DOI:10.1002/cptx.25
PMID:28777439
Abstract

The African clawed frog, Xenopus laevis, has been used as an efficient pre-clinical screening tool to predict drug safety during the early stages of the drug discovery process. X. laevis is a relatively inexpensive model that can be used in whole organism high-throughput assays whilst maintaining a high degree of homology to the higher vertebrate models often used in scientific research. Despite an ever-increasing volume of biomedical nanoparticles (NPs) in development, their unique physico-chemical properties challenge the use of standard toxicology assays. Here, we present a protocol that directly compares the sensitivity of X. laevis development as a tool to assess potential NP toxicity by observation of embryo phenotypic abnormalities/lethality after NP exposure, to in vitro cytotoxicity obtained using mammalian cell lines. In combination with conventional cytotoxicity assays, the X. laevis phenotypic assay provides accurate data to efficiently assess the safety of novel biomedical NPs. © 2017 by John Wiley & Sons, Inc.

摘要

非洲爪蟾(非洲爪蟾,Xenopus laevis)已被用作一种高效的临床前筛选工具,用于在药物发现过程的早期预测药物安全性。非洲爪蟾是一种相对廉价的模型,可用于全生物体高通量分析,同时与科学研究中常用的高等脊椎动物模型保持高度同源性。尽管正在开发的生物医学纳米颗粒(NPs)数量不断增加,但其独特的物理化学性质对标准毒理学分析的应用提出了挑战。在此,我们提出了一种方案,该方案通过观察纳米颗粒暴露后胚胎的表型异常/致死率,直接比较非洲爪蟾发育作为评估潜在纳米颗粒毒性工具的敏感性与使用哺乳动物细胞系获得的体外细胞毒性。与传统的细胞毒性分析相结合,非洲爪蟾表型分析提供了准确的数据,以有效评估新型生物医学纳米颗粒的安全性。© 2017约翰威立国际出版公司

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