Graphene oxide (GO)-based materials are increasingly being used in medical materials and consumer products. However, their sublethal effects on biological systems are poorly understood. Here, we report that GO (at 10 to 160 mg/L) induced significant inhibitory effects on the growth of different unicellular organisms, including eukaryotes (i.e. Saccharomyces cerevisiae, Candida albicans, and Komagataella pastoris) and prokaryotes (Pseudomonas fluorescens). Growth inhibition could not be explained by commonly reported cytotoxicity mechanisms such as plasma membrane damage or oxidative stress. Based on transcriptomic analysis and measurement of extra- and intracellular iron concentrations, we show that the inhibitory effect of GO was mainly attributable to iron deficiency caused by binding to the O-functional groups of GO, which sequestered iron and disrupted iron-related physiological and metabolic processes. This inhibitory mechanism was corroborated with supplementary experiments, where adding bathophenanthroline disulfonate—an iron chelating agent—to the culture medium exerted similar inhibition, whereas removing surface O-functional groups of GO decreased iron sequestration and significantly alleviated the inhibitory effect. These findings highlight a potential indirect detrimental effect of nanomaterials (i.e. scavenging of critical nutrients), and encourage research on potential biomedical applications of GO-based materials to sequester iron and enhance treatment of iron-dependent diseases such as cancer and some pathogenic infections.

中文翻译：

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氧化石墨烯通过引起细胞外铁缺乏而显着抑制亚致死浓度的细胞生长

基于氧化石墨烯（GO）的材料正越来越多地用于医疗材料和消费产品中。但是，它们对生物系统的亚致死作用知之甚少。在这里，我们报道GO（以10至160 mg / L）对不同单细胞生物的生长具有明显的抑制作用，包括真核生物（即酿酒酵母，白色念珠菌和巴斯德Komagataella pastoris）和原核生物（荧光假单胞菌））。不能通过通常报道的细胞毒性机制如质膜损伤或氧化应激来解释生长抑制。基于转录组学分析和细胞外和细胞内铁浓度的测定，我们发现GO的抑制作用主要归因于与GO的O-官能团结合而引起的铁缺乏，螯合了铁并破坏了铁相关的生理和生理功能。代谢过程。补充实验证实了这种抑制机制，在该实验中，向培养基中加入铁螯合剂二邻菲咯啉二磺酸盐也具有类似的抑制作用，而去除GO的表面O-官能团则减少了铁的螯合并显着减轻了抑制作用。