Internalization and cytotoxicity of graphene oxide and carboxyl graphene nanoplatelets in the human hepatocellular carcinoma cell line Hep G2.
Internalization and cytotoxicity of graphene oxide and carboxyl graphene nanoplatelets in the human hepatocellular carcinoma cell line Hep G2.
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DOI：
10.1186/1743-8977-10-27
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发表时间：
2013-07-12
影响因子：
10
通讯作者：
Navas JM
中科院分区：
文献类型：
--
作者：
Lammel T;Boisseaux P;Fernández-Cruz ML;Navas JM
石墨烯和石墨烯衍生物纳米片是新一代纳米材料，具有独特的物理化学性质，在复合材料和生物医学设备中具有很高的应用潜力。迄今为止，人们对意外或故意接触石墨烯纳米材料可能对人体健康造成的影响知之甚少。本研究的目的是评估具有不同表面化学性质的石墨烯纳米血小板对人肝癌细胞系Hep G2的细胞毒性潜力，并确定潜在的毒性靶点。在水和培养基中获得氧化石墨烯（GO）和羧基石墨烯（CXYG）纳米血小板悬浮液。采用动态光散射法测定了悬浮液的尺寸频率分布。利用原子力和电子显微镜测定纳米血小板的高度、横向尺寸和形状。在Hep G2细胞中，使用一系列涵盖不同作用模式的检测来评估氧化石墨烯和CXYG纳米血小板的细胞毒性，包括代谢活性、质膜完整性和溶酶体功能的改变。通过测量细胞内活性氧水平来评估氧化应激的诱导。通过扫描电镜和透射电镜研究了氧化石墨烯和CXYG纳米血小板与质膜的相互作用、内化和细胞内命运。在培养基中添加血清是获得稳定的氧化石墨烯和CXYG悬浮液的必要条件。两种石墨烯衍生物均对质膜具有高亲和力，且在浓度低至4 μg/ml时对质膜造成结构损伤。纳米血小板穿过细胞膜进入细胞质，在那里它们被浓缩并包裹在囊泡中。氧化石墨烯和CXYG在细胞质中的积累伴随着细胞内活性氧（ROS）水平的增加、细胞超微结构的改变和代谢活性的变化。氧化石墨烯和CXYG纳米血小板在Hep G2细胞中引起剂量和时间依赖性的细胞毒性，质膜损伤和诱导氧化应激是毒性的重要模式。两种石墨烯衍生物都被Hep G2（一种非吞噬细胞系）内化。此外，当极低浓度（< 4 μg/ml）施用时，它们没有毒性。因此，氧化石墨烯和CXYG纳米血小板可能是一种有吸引力的生物医学应用材料。
Graphene and graphene derivative nanoplatelets represent a new generation of nanomaterials with unique physico-chemical properties and high potential for use in composite materials and biomedical devices. To date little is known about the impact graphene nanomaterials may have on human health in the case of accidental or intentional exposure. The objective of this study was to assess the cytotoxic potential of graphene nanoplatelets with different surface chemistry towards a human hepatoma cell line, Hep G2, and identify the underlying toxicity targets. Graphene oxide (GO) and carboxyl graphene (CXYG) nanoplatelet suspensions were obtained in water and culture medium. Size frequency distribution of the suspensions was determined by means of dynamic light scattering. Height, lateral dimension and shape of the nanoplatelets were determined using atomic force and electron microscopy. Cytotoxicity of GO and CXYG nanoplatelets was assessed in Hep G2 cells using a battery of assays covering different modes of action including alterations of metabolic activity, plasma membrane integrity and lysosomal function. Induction of oxidative stress was assessed by measuring intracellular reactive oxygen species levels. Interaction with the plasma membrane, internalization and intracellular fate of GO and CXYG nanoplatelets was studied by scanning and transmission electron microscopy. Supplementing culture medium with serum was essential to obtain stable GO and CXYG suspensions. Both graphene derivatives had high affinity for the plasma membrane and caused structural damage of the latter at concentrations as low as 4 μg/ml. The nanoplatelets penetrated through the membrane into the cytosol, where they were concentrated and enclosed in vesicles. GO and CXYG accumulation in the cytosol was accompanied by an increase in intracellular reactive oxygen species (ROS) levels, alterations in cellular ultrastructure and changes in metabolic activity. GO and CXYG nanoplatelets caused dose- and time-dependent cytotoxicity in Hep G2 cells with plasma membrane damage and induction of oxidative stress being important modes of toxicity. Both graphene derivatives were internalized by Hep G2, a non-phagocytotic cell line. Moreover, they exerted no toxicity when applied at very low concentrations (< 4 μg/ml). GO and CXYG nanoplatelets may therefore represent an attractive material for biomedical applications.
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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：
29.4
作者：
Hu, Shang-Hsiu;Chen, Yu-Wei;Chen, San-Yuan
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影响因子：
3.2
作者：
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通讯作者：
Tarloff, JB
DOI：
10.1007/1-4020-3120-3_16
发表时间：
2005-01-01
期刊：
SMALL -SCALE FRESHWATER TOXICITY INVESTIGATIONS, VOL 1 - TOXICITY TEST METHODS
影响因子：
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作者：
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通讯作者：
Bols, Niels C.
影响因子：
13.3
作者：
Bao, Hongqian;Pan, Yongzheng;Gan, Leong Huat
通讯作者：
Gan, Leong Huat