Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model.
Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model.
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氧化石墨烯的表面氧化决定肺毒性模型中巨噬细胞的膜损伤、脂质过氧化和细胞毒性
DOI：
10.1021/acsnano.7b07737
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发表时间：
2018-02-27
期刊：
影响因子：
17.1
通讯作者：
Xia T
中科院分区：
文献类型：
--
作者：
Li R;Guiney LM;Chang CH;Mansukhani ND;Ji Z;Wang X;Liao YP;Jiang W;Sun B;Hersam MC;Nel AE;Xia T
虽然二维氧化石墨烯（GO）越来越多地用于生物医学应用，但具体的物理化学性质与哺乳动物系统中的生物相容性之间的关系尚不确定。虽然纳米片的横向尺寸和胶体性质等性质很重要，但我们在这里讨论的具体材料性质是平面表面上的氧化态和反应性表面基团。在这项研究中，我们使用了GO库，包括原始的，还原的（rGO），和水合GO（hGO），其中羟基，羧基，环氧基和碳自由基含量的定量评估用于研究对上皮细胞和巨噬细胞的影响，以及在小鼠肺。引人注目的是，我们观察到，hGO，其表现出最高的碳自由基密度，是负责在THP-1和BEAS-2B细胞中的细胞死亡的产生作为结果的表面膜的脂质过氧化，膜溶解，和细胞死亡。相比之下，原始GO具有较小的影响，而rGO显示出广泛的细胞摄取，对活力的影响最小。为了观察这些体外效应如何与肺中的不良结果相关，通过口咽抽吸将小鼠暴露于顺铂。40 h后处死动物表明，hGO比其他材料更容易产生急性肺部炎症，伴有肺泡巨噬细胞中最高的脂质过氧化反应，支气管肺泡灌洗液中细胞因子（LIX，MCP-1）和LDH的释放。原始GO显示出较低的毒性，而rGO具有最小的影响。总之，我们证明了表面氧化态和碳自由基含量在哺乳动物细胞和肺中GO诱导毒性中起主要作用。
While 2-dimensional graphene oxide (GO) is used increasingly in biomedical applications, there is uncertainty on how specific physicochemical properties relate to biocompatibility in mammalian systems. Although properties such as lateral size and the colloidal properties of the nanosheets are important, the specific material properties that we address here is the oxidation state and reactive surface groups on the planar surface. In this study, we used a GO library, comprised of pristine, reduced (rGO), and hydrated GO (hGO), in which quantitative assessment of the hydroxyl, carboxyl, epoxy and carbon radical contents were used to study the impact on epithelial cells and macrophages, as well as in the murine lung. Strikingly, we observed that hGO, which exhibits the highest carbon radical density, was responsible for the generation of cell death in THP-1 and BEAS-2B cells as a consequence of lipid peroxidation of the surface membrane, membrane lysis, and cell death. In contrast, pristine GO had lesser effects while rGO showed extensive cellular uptake with minimal effects on viability. In order to see how these in vitro effects relate to adverse outcomes in the lung, mice were exposed to GOs by oropharyngeal aspiration. Animal sacrifice after 40h demonstrated that hGO was more prone than other materials in generating acute lung inflammation, accompanied by the highest lipid peroxidation in alveolar macrophages, cytokine production (LIX, MCP-1) and LDH release in bronchoalveolar lavage fluid. Pristine GO showed less toxicity while rGO had minimal effects. In summary, we demonstrate that the surface oxidation state and carbon radical content play major roles in the induction of toxicity by GO in mammalian cells and the lung.
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影响因子：
10
作者：
Lammel T;Boisseaux P;Fernández-Cruz ML;Navas JM
通讯作者：
Navas JM
影响因子：
17.1
作者：
Liu, Shaobin;Zeng, Tingying Helen;Chen, Yuan
通讯作者：
Chen, Yuan
蛋白质涂层氧化石墨烯纳米片的尺寸依赖性细胞摄取
影响因子：
9.5
作者：
Mu, Qingxin;Su, Gaoxing;Yan, Bing
通讯作者：
Yan, Bing
影响因子：
0.9
作者：
Azimi, Sara;Behin, Jamshid;Karimnezhad, Hanieh
通讯作者：
Karimnezhad, Hanieh
氧化石墨烯的新功能出现：灭活植物病原菌米黄单胞菌。
影响因子：
2.5
作者：
Chen, Juanni;Wang, Xiuping;Han, Heyou
通讯作者：
Han, Heyou