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用于可靠毒性评估的纳米材料物理化学表征的首要性:斑马鱼纳米毒理学模型综述

The primacy of physicochemical characterization of nanomaterials for reliable toxicity assessment: a review of the zebrafish nanotoxicology model.

作者信息

Bohnsack John P, Assemi Shoeleh, Miller Jan D, Furgeson Darin Y

机构信息

Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA.

出版信息

Methods Mol Biol. 2012;926:261-316. doi: 10.1007/978-1-62703-002-1_19.

Abstract

Engineered nanomaterials (ENMs) have become increasingly prevalent in the past two decades in academic, medical, commercial, and industrial settings. The unique properties imbued with nanoparticles, as the physiochemical properties change from the bulk material to the surface atoms, present unique and often challenging characteristics that larger macromolecules do not possess. While nanoparticle characteristics are indeed exciting for unique chemistries, surface properties, and diverse applications, reports of toxicity and environmental impacts have tempered this enthusiasm and given cause for an exponential increase for concomitant nanotoxicology assessment. Currently, nanotoxicology is a steadily growing with new literature and studies being published more frequently than ever before; however, the literature reveals clear, inconsistent trends in nanotoxicological assessment. At the heart of this issue are several key problems including the lack of validated testing protocols and models, further compounded by inadequate physicochemical characterization of the nanomaterials in question and the seminal feedback loop of chemistry to biology back to chemistry. Zebrafish (Danio rerio) are emerging as a strong nanotoxicity model of choice for ease of use, optical transparency, cost, and high degree of genomic homology to humans. This review attempts to amass all contemporary nanotoxicology studies done with the zebrafish and present as much relevant information on physicochemical characteristics as possible. While this report is primarily a physicochemical summary of nanotoxicity studies, we wish to strongly emphasize that for the proper evolution of nanotoxicology, there must be a strong marriage between the physical and biological sciences. More often than not, nanotoxicology studies are reported by groups dominated by one discipline or the other. Regardless of the starting point, nanotoxicology must be seen as an iterative process between chemistry and biology. It is our sincere hope that the future will introduce a paradigm shift in the approach to nanotoxicology with multidisciplinary groups for data analysis to produce predictive and correlative models for the end goal of rapid preclinical development of new therapeutics into the clinic or insertion into environmental protection.

摘要

在过去二十年中,工程纳米材料(ENMs)在学术、医学、商业和工业领域越来越普遍。纳米颗粒具有独特的性质,因为其物理化学性质从块状材料转变为表面原子,呈现出大分子所不具备的独特且往往具有挑战性的特性。虽然纳米颗粒的特性确实因其独特的化学性质、表面性质和多样的应用而令人兴奋,但关于毒性和环境影响的报告削弱了这种热情,并导致伴随的纳米毒理学评估呈指数级增长。目前,纳米毒理学随着新文献和研究的发表比以往任何时候都更加频繁而稳步发展;然而,文献揭示了纳米毒理学评估中明显且不一致的趋势。这个问题的核心是几个关键问题,包括缺乏经过验证的测试方案和模型,而相关纳米材料的物理化学表征不足以及从化学到生物学再回到化学的关键反馈循环进一步加剧了这一问题。斑马鱼(Danio rerio)因其易于使用、光学透明、成本低以及与人类高度的基因组同源性,正成为一种强大的纳米毒性模型选择。本综述试图收集所有用斑马鱼进行的当代纳米毒理学研究,并尽可能呈现有关物理化学特性的相关信息。虽然本报告主要是纳米毒性研究的物理化学总结,但我们强烈强调,为了纳米毒理学的正确发展,物理科学和生物科学之间必须紧密结合。纳米毒理学研究通常由以某一学科为主导的团队报告。无论从哪个起点开始,纳米毒理学都必须被视为化学和生物学之间的一个迭代过程。我们真诚地希望,未来纳米毒理学的研究方法会发生范式转变,多学科团队进行数据分析,以产生预测性和相关性模型,最终目标是将新疗法快速推进到临床前开发阶段并应用于临床,或用于环境保护。

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