Shifts in oxidation states of cerium oxide nanoparticles detected inside intact hydrated cells and organelles.

Shifts in oxidation states of cerium oxide nanoparticles detected inside intact hydrated cells and organelles.
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DOI:
10.1016/j.biomaterials.2015.05.042
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发表时间:
2015-09
期刊:
影响因子:
14
通讯作者:
Orr, Galya
Orr, Galya
中科院分区:
工程技术1区
文献类型:
--
作者:
Szymanski, Craig J.;Munusamy, Prabhakaran;Mihai, Cosmin;Xie, Yumei;Hu, Dehong;Gilles, Mary K.;Tyliszczak, Tolek;Thevuthasan, Suntharampillai;Baer, Donald R.;Orr, Galya

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氧化铈纳米颗粒(CNP)已被证明可诱导多种生物效应,从有毒到有益。有益效果归因于CNP通过某些氧化还原反应的潜在抗氧化活性,这取决于它们的氧化态或Ce 3 +/Ce 4+比。然而,该比率强烈依赖于纳米颗粒的环境和年龄,并且尚不清楚复杂的细胞内环境是否以及如何影响该比率和CNP的可能的氧化还原反应。为了识别胞内环境中CNPs氧化态的任何变化并更好地了解其胞内反应,我们使用相关扫描透射X射线和超分辨率荧光显微镜直接量化完整水合细胞和细胞器外部和内部CNPs的氧化态。通过分析数百个小CNP聚集体,我们检测到细胞内与细胞外CNP中的Ce 3 +/Ce 4+比率向更高的转变,表明细胞内环境中CNP的净减少。我们进一步发现,在细胞质和溶酶体中的比例相似,表明净减少发生在内化途径的早期。结合氧化应激和毒性测量,我们的观察结果确定了细胞内环境中CNP的净减少,这与它们参与潜在有益的氧化反应一致,但也指出了可能对细胞健康产生负面影响的相互作用。
Cerium oxide nanoparticles (CNPs) have been shown to induce diverse biological effects, ranging from toxic to beneficial. The beneficial effects have been attributed to the potential antioxidant activity of CNPs via certain redox reactions, depending on their oxidation state or Ce3+/Ce4+ ratio. However, this ratio is strongly dependent on the environment and age of the nanoparticles and it is unclear whether and how the complex intracellular environment impacts this ratio and the possible redox reactions of CNPs. To identify any changes in the oxidation state of CNPs in the intracellular environment and better understand their intracellular reactions, we directly quantified the oxidation states of CNPs outside and inside intact hydrated cells and organelles using correlated scanning transmission x-ray and super resolution fluorescence microscopies. By analyzing hundreds of small CNP aggregates, we detected a shift to a higher Ce3+/Ce4+ ratio in CNPs inside versus outside the cells, indicating a net reduction of CNPs in the intracellular environment. We further found a similar ratio in the cytoplasm and in the lysosomes, indicating that the net reduction occurs earlier in the internalization pathway. Together with oxidative stress and toxicity measurements, our observations identify a net reduction of CNPs in the intracellular environment, which is consistent with their involvement in potentially beneficial oxidation reactions, but also point to interactions that can negatively impact the health of cells.
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