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对 U87 神经胶质瘤细胞和肿瘤以及 HS-5 细胞的原始石墨烯毒性的主要机制为线粒体降解和氧化应激。

Degradation of Mitochondria and Oxidative Stress as the Main Mechanism of Toxicity of Pristine Graphene on U87 Glioblastoma Cells and Tumors and HS-5 Cells.

机构信息

Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, 02-786 Warsaw, Poland.

Department of Veterinary and Animal Sciences, Groennegaardsvej 3, 1870 Frederiksberg, Denmark.

出版信息

Int J Mol Sci. 2019 Feb 2;20(3):650. doi: 10.3390/ijms20030650.

Abstract

Due to the development of nanotechnologies, graphene and graphene-based nanomaterials have attracted immense scientific interest owing to their extraordinary properties. Graphene can be used in many fields, including biomedicine. To date, little is known about the impact graphene may have on human health in the case of intentional exposure. The present study was carried out on U87 glioma cells and non-cancer HS-5 cell lines as in vitro model and U87 tumors cultured on chicken embryo chorioallantoic membrane as in vivo model, on which the effects of pristine graphene platelets (GPs) were evaluated. The investigation consisted of structural analysis of GPs using transmission electron microscopy, Fourier transmission infrared measurements, zeta potential measurements, evaluation of cell morphology, assessment of cell viability, investigation of reactive oxygen species production, and investigation of mitochondrial membrane potential. The toxicity of U87 glioma tumors was evaluated by calculating the weight and volume of tumors and performing analyses of the ultrastructure, histology, and protein expression. The in vitro results indicate that GPs have dose-dependent cytotoxicity via ROS overproduction and depletion of the mitochondrial membrane potential. The mass and volume of tumors were reduced in vivo after injection of GPs. Additionally, the level of apoptotic and necrotic markers increased in GPs-treated tumors.

摘要

由于纳米技术的发展,石墨烯和基于石墨烯的纳米材料因其非凡的特性而引起了科学界的极大兴趣。石墨烯可以用于许多领域,包括生物医药。迄今为止,人们对故意暴露于石墨烯时其可能对人类健康产生的影响知之甚少。本研究以 U87 神经胶质瘤细胞和非癌细胞 HS-5 细胞系作为体外模型,以鸡胚尿囊膜上培养的 U87 肿瘤作为体内模型,评估了原始石墨烯片(GPs)的作用。该研究包括使用透射电子显微镜、傅里叶传输红外测量、zeta 电位测量对 GPs 进行结构分析,评估细胞形态,评估细胞活力,研究活性氧的产生,以及研究线粒体膜电位。通过计算肿瘤的重量和体积以及进行超微结构、组织学和蛋白质表达分析来评估 U87 神经胶质瘤肿瘤的毒性。体外结果表明,GPs 通过过量产生 ROS 和耗尽线粒体膜电位表现出剂量依赖性细胞毒性。注射 GPs 后,体内肿瘤的质量和体积减少。此外,在 GPs 处理的肿瘤中,凋亡和坏死标志物的水平增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/863a/6386908/8b9056f74542/ijms-20-00650-g001.jpg

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