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细胞毒理学过程中纳米材料的分析方法
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摘要
纳米材料从暴露到产生细胞毒性,涵盖了生物分子吸附、降解、催化、氧化还原等物理化学过程。阐明毒理学的化学机制,需解决纳米材料分析难题,以实现生物体系中纳米材料的精确定位、准确定量分析。针对这些分析难题,我们以同步辐射等技术为基础,发展了原位、灵敏的定量与定位分析方法,系统地研究了毒理学效应并阐明机制。建立纳米材料与蛋白质吸附界面结构的解析及成像方法,揭示蛋白质稳定吸附于纳米材料表面可降低毒性的规律~([1])。提出以化学形态为基础来实现金属纳米材料可靠成像的策略,并发展三维高分辨单细胞成像方法,阐明纳米材料化学转化、自由基产生等协同诱导毒性的机制~([2-3])。发展纳米材料催化过程中自由基测定与成像方法,阐明自由基调控细胞信号通路,实现细胞对化疗药物增敏机制~([4])。这些创新的分析方法,为纳米毒理学机制研究提供了准确、可靠的化学形态、结构、成像信息,将为纳米生物医学研究提供重要的分析方法。
It is a challenge to uncover how nanomaterials induce cytotoxicity because accurate and in situ analytical techniques lack in studying chemical processes including biomolecule adsorption, degradation, catalysis, and redox. To reveal cytotoxicity mechanism, we developed in situ and sensitive methods to quantify nanomaterials and capture their location inside cells. First, novel methods were used to characterize binding structure of proteins on nanomaterials and to image intracellular protein-nanomaterial complex, which revealed that the stably adsorbed proteins can reduce cytotoxicity. Second, we proposed that accurate imaging for intracellular metal nanomaterials relies on their chemical forms, by which 3D and high resolution imaging for nanomaterials was realized to explore cytotoxicity mechanism. Third, we developed methods to characterize nanomaterial-involved photo-catalysis in biological systems and showed how free radicals mediate cell signaling pathway. In conclusion, these techniques provide accurate information for chemical forms, structures, and element imaging with promises in nanotoxicology and nanomedicine.
引文
[1]Wang,L.;Li,J.;Pan,J.;Chen,C.,et al.J.Am.Chem.Soc.2013,135:17359.
    [2]Wang,L.;Zhang,T.;Zhao,Y.;Chen,C.,et al.ACS Nano 2015,9:6532.
    [3]Liu,J.;Wang,L.;Liu,Y.;Chen,C.,et al.ACS Nano 2016,DOI:10.1021/acsnano.6b00745
    [4]Wang,L.;Sun,Q.;Lu,A.;Chen,C.,et al.J.Am.Chem.Soc.2015,137:1947.

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