Crucial Role of Lateral Size for Graphene Oxide in Activating Macrophages and Stimulating Pro-inflammatory Responses in Cells and Animals.
Crucial Role of Lateral Size for Graphene Oxide in Activating Macrophages and Stimulating Pro-inflammatory Responses in Cells and Animals.
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氧化石墨烯横向尺寸在激活细胞和动物巨噬细胞和刺激促炎反应中的关键作用
DOI：
10.1021/acsnano.5b04751
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发表时间：
2015-10-27
期刊：
影响因子：
17.1
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Ma J;Liu R;Wang X;Liu Q;Chen Y;Valle RP;Zuo YY;Xia T;Liu S
氧化石墨烯（GO）越来越多地用于生物医学应用，因为它不仅具有石墨烯的独特性质，包括大表面积和柔韧性，而且还具有亲水性和在水溶液中的分散性。然而，其生物相容性和生物安全性存在相互矛盾的结果，部分原因是GO的理化性质存在巨大差异，并且这些性质（包括横向尺寸）在GO的生物或毒理学效应中的作用仍不清楚。在这项研究中，我们通过使用相同的起始材料制备一组具有不同横向尺寸的 GO 样品，重点关注横向尺寸的作用。我们发现，与较小的 GO 相比，较大的 GO 在质膜上表现出更强的吸附作用，而吞噬作用较少，从而引发与 Toll 样受体更强烈的相互作用，并更有效地激活 NF-κB 通路。相比之下，较小的GO片更有可能被细胞占据。因此，较大的 GO 促进了更大的 M1 极化，这与炎症细胞因子的产生增强和免疫细胞的募集有关。体外结果与 GO 通过尾静脉注入腹腔、肺或血流后的局部和全身炎症反应密切相关。总之，我们的研究描述了巨噬细胞大小依赖性的 M1 诱导以及体外和体内 GO 的促炎症反应。我们的数据还揭示了这些效应背后的详细机制：GO 和质膜之间依赖于尺寸的相互作用。
Graphene oxide (GO) is increasingly used in biomedical applications because it possesses not only the unique properties of graphene including large surface area and flexibility but also hydrophilicity and dispersibility in aqueous solutions. However, there are conflicting results on its biocompatibility and biosafety partially due to large variations in physicochemical properties of GO, and the role of these properties including lateral size in the biological or toxicological effects of GO is still unclear. In this study, we focused on the role of lateral size by preparing a panel of GO samples with differential lateral sizes using the same starting material. We found that, in comparison to its smaller counterpart, larger GO showed a stronger adsorption onto the plasma membrane with less phagocytosis, which elicited more robust interaction with toll-like receptors and more potent activation of NF-κB pathways. By contrast, smaller GO sheets were more likely taken up by cells. As a result, larger GO promoted greater M1 polarization, associated with enhanced production of inflammatory cytokines and recruitment of immune cells. The in vitro results correlated well with local and systemic inflammatory responses after GO administration into the abdominal cavity, lung, or bloodstream through the tail vein. Together, our study delineated the size-dependent M1 induction of macrophages and pro-inflammatory responses of GO in vitro and in vivo. Our data also unearthed the detailed mechanism underlying these effects: a size-dependent interaction between GO and the plasma membrane.
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影响因子：
5.6
作者：
Hoppstädter J;Seif M;Dembek A;Cavelius C;Huwer H;Kraegeloh A;Kiemer AK
通讯作者：
Kiemer AK
影响因子：
8
作者：
Gurunathan S;Han JW;Dayem AA;Eppakayala V;Kim JH
通讯作者：
Kim JH
石墨烯在生物医学中的机遇与挑战
影响因子：
5.5
作者：
Feng, Liangzhu;Liu, Zhuang
通讯作者：
Liu, Zhuang
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
17.1
作者：
Cho, Won Joon;Kim, Youngsuk;Kim, Jin Kon
通讯作者：
Kim, Jin Kon