College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, EX4 4QF, United Kingdom.
Nanotechnology. 2017 Dec 15;28(50):504001. doi: 10.1088/1361-6528/aa95a8.
The intriguing properties of reduced graphene oxide (rGO) have paved the way for a number of potential biomedical applications such as drug delivery, tissue engineering, gene delivery and bio-sensing. Over the last decade, there have been escalating concerns regarding the possible toxic effects, behaviour and fate of rGO in living systems and environments. This paper reports on integrative chemical-biological interactions of rGO with lung cancer cells, i.e. A549 and SKMES-1, to determine its potential toxicological impacts on them, as a function of its concentration. Cell viability, early and late apoptosis and necrosis were measured to determine oxidative stress potential, and induction of apoptosis for the first time by comparing two lung cancer cells. We also showed the general trend between cell death rates and concentrations for different cell types using a Gaussian process regression model. At low concentrations, rGO was shown to significantly produce late apoptosis and necrosis rather than early apoptotic events, suggesting that it was able to disintegrate the cellular membranes in a dose dependent manner. For the toxicity exposures undertaken, late apoptosis and necrosis occurred, which was most likely resultant from limited bioavailability of unmodified rGO in lung cancer cells.
还原氧化石墨烯(rGO)的有趣性质为许多潜在的生物医学应用铺平了道路,例如药物传递、组织工程、基因传递和生物传感。在过去的十年中,人们越来越关注 rGO 在活系统和环境中的可能毒性作用、行为和命运。本文报告了 rGO 与肺癌细胞(即 A549 和 SKMES-1)的综合化学-生物学相互作用,以确定其对它们的潜在毒理学影响,这是其浓度的函数。细胞活力、早期和晚期细胞凋亡和坏死被测量以确定氧化应激潜力,并首次通过比较两种肺癌细胞来诱导细胞凋亡。我们还使用高斯过程回归模型显示了不同细胞类型的细胞死亡率和浓度之间的一般趋势。在低浓度下,rGO 明显产生晚期细胞凋亡和坏死,而不是早期细胞凋亡事件,这表明它能够以剂量依赖的方式破坏细胞膜。对于所进行的毒性暴露,晚期细胞凋亡和坏死发生了,这很可能是由于未修饰的 rGO 在肺癌细胞中的生物利用度有限所致。