Graphene quantum dots in alveolar macrophage: uptake-exocytosis,accumulation in nuclei,nuclear responses and DNA cleavage

Background

Given the tremendous potential for graphene quantum dots (QDs) in biomedical applications, a thorough understanding of the interaction of these materials with macrophages is essential because macrophages are one of the most important barriers against exogenous particles. Although the cytotoxicity and cellular uptake of graphene QDs were reported in previous studies, the interaction between nuclei and the internalized graphene QDs is not well understood. We thus systematically studied the nuclear uptake and related nuclear response associated with aminated graphene QDs (AG-QDs) exposure.

Results

AG-QDs showed modest 24-h inhibition to rat alveolar macrophages (NR8383), with a minimum inhibitory concentration (MIC) of 200 μg/mL. Early apoptosis was significantly increased by AG-QDs (100 and 200 μg/mL) exposure and played a major role in cell death. The internalization of AG-QDs was mainly via energy-dependent endocytosis, phagocytosis and caveolae-mediated endocytosis. After a 48-h clearance period, more than half of the internalized AG-QDs remained in the cellular cytoplasm and nucleus. Moreover, AG-QDs were effectively accumulated in nucleus and were likely regulated by two nuclear pore complexes genes (Kapβ2 and Nup98). AG-QDs were shown to alter the morphology, area, viability and nuclear components of exposed cells. Significant cleavage and cross-linking of DNA chains after AG-QDs exposure were confirmed by atomic force microscopy investigation. Molecular docking simulations showed that H-bonding and π-π stacking were the dominant forces mediating the interactions between AG-QDs and DNA, and were the important mechanisms resulting in DNA chain cleavage. In addition, the generation of reactive oxygen species (ROS) (e.g., ?OH), and the up-regulation of caspase genes also contributed to DNA cleavage.

Conclusions

AG-QDs were internalized by macrophages and accumulated in nuclei, which further resulted in nuclear damage and DNA cleavage. It is demonstrated that oxidative damage, direct contact via H-bonding and π-π stacking, and the up-regulation of caspase genes are the primary mechanisms for the observed DNA cleavage by AG-QDs.

     

聚乙二醇介质中纳米Fe-Mn催化剂的F-T合成反应性能

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Shear wave velocity and geotechnical properties of tailings deposits

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宝山:规划建设中的现代化滨江新区

1区域性质、规模和发展目标1.1区域性质上海北翼连接长江三角洲沿江城市发展带上的重要门户;世界级精品钢制造以及物流等相关产业集聚辐射区;上海国际航运中心的重要组成部分;生态、生活、     

Sorption of aromatic organic contaminants by biopolymers: effects of pH, copper (II) complexation, and cellulose coating

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对４个厂家生产的１８７０ｄｔｅｘ／２尼龙浸胶帘布进行了压延、裁断、轮胎成品等方面的性能测定及比较。结果表明,帘线由原线到覆胶帘线以及在成品外胎中,其物理性能均发生变化,断裂强力、断裂伸长率及定负荷伸长率均呈下降趋势,各厂家帘线各具特点．     

采用国产化GK400型密炼机的投资效益

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聚丙烯酸盐增稠剂的合成及应用

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