Graphene oxide significantly inhibits cell growth at sublethal concentrations by causing extracellular iron deficiency

Abstract

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.

Keywords:

• Graphene oxide
• iron deficiency
• transcription profiling
• sublethal concentration
• growth inhibition

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project was supported by the National Natural Science Foundation of China (Grants 21237002 and 31400132), the Ministry of Science and Technology of China (Grant 2014CB932001), and the National Science Fund for Distinguished Young Scholars (Grant 21425729). Partial funding was also provided by the NSF ERC on Nanotechnology-Enabled Water Treatment (EEC-1449500). The authors declare no competing financial interests.