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

References

• Akhavan, O., and E. Ghaderi. 2010. “Toxicity of Graphene and Graphene Oxide Nanowalls Against Bacteria.” ACS nano 4: 5731–5736.
   PubMed Web of Science ®Google Scholar
• Beinert, H., and M. C. Kennedy. 1993. “Aconitase, a Two-faced Protein: Enzyme and Iron Regulatory Factor.” FASEB journal: official publication of the federation of american societies for experimental biology 7: 1442–1449.
   PubMed Web of Science ®Google Scholar
• Beinert, H., M. C. Kennedy, and C. D. Stout. 1996. “Aconitase as Iron-sulfur Protein, Enzyme, and Iron-regulatory Protein.” Chemical reviews 96: 2335–2374.
   PubMed Web of Science ®Google Scholar
• Bianco, A. 2013. “Graphene: Safe or Toxic? The Two Faces of the Medal.” Angewandte chemie (International ed. in english) 52: 4986–4997.
   PubMed Web of Science ®Google Scholar
• Bulcke, F., K. Thiel, and R. Dringen. 2014. “Uptake and Toxicity of Copper Oxide Nanoparticles in Cultured Primary Brain Astrocytes.” Nanotoxicology 8: 775–785.
   PubMed Web of Science ®Google Scholar
• Buriak, J. M., and C. Toro. 2015. “Layer-by-layer Growth of Graphene Oxide-based Films for Electronics Applications in 1999: Early Leaders.” Chemistry of materials 27: 1–2.
   Web of Science ®Google Scholar
• Carpio, I. E. M., C. M. Santos, X. Wei, and D. F. Rodrigues. 2012. “Toxicity of a Polymer–graphene Oxide Composite Against Bacterial Planktonic Cells, Biofilms, and Mammalian Cells.” Nanoscale 4: 4746–4756.
   PubMed Web of Science ®Google Scholar
• Chatterjee, N., Y. H. Kim, J. Yang, C. P. Roca, S. W. Joo, and J. Choi. 2017. “A Systems Toxicology Approach Reveals the Wnt-MAPK Crosstalk Pathway Mediated Reproductive Failure in Caenorhabditis elegans Exposed to Graphene Oxide (GO) but Not to Reduced Graphene Oxide (rGO).” Nanotoxicology 11: 1–39.
   PubMed Web of Science ®Google Scholar
• Chen, Y., X. Hu, J. Sun, and Q. Zhou. 2016. “Specific Nanotoxicity of Graphene Oxide During Zebrafish Embryogenesis.” Nanotoxicology 10: 42–52.
   PubMed Web of Science ®Google Scholar
• Chung, C., Y. K. Kim, D. Shin, S. R. Ryoo, B. H. Hong, and D. H. Min. 2013. “Biomedical Applications of Graphene and Graphene Oxide.” Accounts of chemical research 46: 2211–2224.
   PubMed Web of Science ®Google Scholar
• Compton, O. C., and S. T. Nguyen. 2010. “Graphene Oxide, Highly Reduced Graphene Oxide, and Graphene: Versatile Building Blocks for Carbon-based Materials.” Small (Weinheim an der bergstrasse, Germany) 6: 711–723.
   PubMed Web of Science ®Google Scholar
• Dreyer, D. R., S. Park, C. W. Bielawski, and R. S. Ruoff. 2010. “The Chemistry of Graphene Oxide.” Chemical society reviews 39: 228–240.
   PubMed Web of Science ®Google Scholar
• Ema, M., K. S. Hougaard, A. Kishimoto, and K. Honda. 2016. “Reproductive and Developmental Toxicity of Carbon-based Nanomaterials: a Literature Review.” Nanotoxicology 10: 391–412.
   PubMed Web of Science ®Google Scholar
• Fafournoux, P., A. Bruhat, and C. Jousse. 2000. “Amino Acid Regulation of Gene Expression.” The biochemical journal 351: 1–12.
   PubMed Web of Science ®Google Scholar
• Feng, M., H. Kang, Z. Yang, B. Luan, and R. Zhou. 2016. “Potential Disruption of Protein-protein Interactions by Graphene Oxide.” The journal of chemical physics 144: 225102.
   PubMed Web of Science ®Google Scholar
• Frost, R., S. Svedhem, C. Langhammer, and B. Kasemo. 2016. “Graphene Oxide and Lipid Membranes: Size-dependent Interactions.” Langmuir: The acs journal of surfaces and colloids 32: 2708–2717.
   PubMed Web of Science ®Google Scholar
• Gao, Y., J. Wu, X. Ren, X. Tan, T. Hayat, A. Alsaedi, C. Cheng, and C. Chen. 2017b. “Impact of Graphene Oxide on the Antibacterial Activity of Antibiotics Against Bacteria.” Environmental science: Nano 4: 1016–1024.
   Web of Science ®Google Scholar
• Gao, Y., X. Ren, X. Tan, T. Hayat, A. Alsaedi, and C. Chen. 2017a. “Insights into Key Factors Controlling GO Stability in Natural Surface Waters.” Journal of hazardous materials 335: 56–65.
   PubMed Web of Science ®Google Scholar
• Gottschalk, F., T. Sun, and B. Nowack. 2013. “Environmental Concentrations of Engineered Nanomaterials: Review of Modeling and Analytical Studies.” Environmental pollution (Barking, essex: 1987) 181: 287–300.
   PubMed Web of Science ®Google Scholar
• Gou, N., A. Onnis-Hayden, and A. Z. Gu. 2010. “Mechanistic Toxicity Assessment of Nanomaterials by Whole-cell-array Stress Genes Expression Analysis.” Environmental science & technology 44: 5964–5970.
   PubMed Web of Science ®Google Scholar
• Guo, L., A. Von Dem Bussche, M. Buechner, A. Yan, A. B. Kane, and R. H. Hurt. 2008. “Adsorption of Essential Micronutrients by Carbon Nanotubes and the Implications for Nanotoxicity Testing.” Small (Weinheim an der bergstrasse, Germany) 4: 721–727.
   PubMed Web of Science ®Google Scholar
• Hernandez-Viezcas, J. A., H. Castillo-Michel, J. R. Peralta-Videa, and J. L. Gardea-Torresdey. 2016. “Interactions Between CeO2 Nanoparticles and the Desert Plant Mesquite: a Spectroscopy Approach.” ACS sustainable chemistry & engineering 4: 1187–1192.
   Web of Science ®Google Scholar
• Hoecke, K. V., J. T. Quik, J. Mankiewicz-Boczek, K. A. D. Schamphelaere, A. Elsaesser, P. V. D. Meeren, and K. Rydzynski. 2009. “Fate and Effects of CeO2 Nanoparticles in Aquatic Ecotoxicity Tests.” Environmental science & technology 43: 4537–4546.
   PubMed Web of Science ®Google Scholar
• Hummers, W. S., Jr, and R. E. Offeman. 1958. “Preparation of Graphitic Oxide.” Journal of the american chemical society 80: 1339–1339.
   Web of Science ®Google Scholar
• Iversen, T. G., T. Skotland, and K. Sandvig. 2011. “Endocytosis and Intracellular Transport of Nanoparticles: Present Knowledge and Need for Future Studies.” Nano today 6: 176–185.
   Web of Science ®Google Scholar
• Kiser, M. A., P. Westerhoff, T. Benn, Y. Wang, J. Perez-Rivera, and K. Hristovski. 2009. “Titanium Nanomaterial Removal and Release from Wastewater Treatment Plants.” Environmental science & technology 43: 6757–6763.
   PubMed Web of Science ®Google Scholar
• Kollár, R., E. Petráková, G. Ashwell, P. W. Robbins, and E. Cabib. 1995. “Architecture of the Yeast Cell Wall. The Linkage Between Chitin and Beta(1,3)-Glucan.” The journal of biological chemistry 270: 1170–1178.
   PubMed Web of Science ®Google Scholar
• Lefevre, E., N. Bossa, M. R. Wiesner, and C. K. Gunsch. 2016. “A Review of the Environmental Implications of In Situ Remediation by Nanoscale Zero Valent Iron (nZVI): Behavior, Transport and Impacts on Microbial Communities.” The science of the total environment 565: 889–901.
   PubMed Web of Science ®Google Scholar
• Li, J., G. Wang, H. Zhu, M. Zhang, X. Zheng, Z. Di, and X. Wang. 2014. “Antibacterial Activity of Large-area Monolayer Graphene Film Manipulated By Charge Transfer.” Scientific reports 4: 4359.
   PubMed Web of Science ®Google Scholar
• Liang, S., S. Xu, D. Zhang, J. He, and M. Chu. 2015. “Reproductive Toxicity of Nanoscale Graphene Oxide in Male Mice.” Nanotoxicology 9: 92–105.
   PubMed Web of Science ®Google Scholar
• Lill, R., and U. Mühlenhoff. 2008. “Maturation of Iron-sulfur Proteins in Eukaryotes: Mechanisms, Connected Processes, and Diseases.” Annual review of biochemistry 77: 669–700.
   PubMed Web of Science ®Google Scholar
• Liu, S., T. H. Zeng, M. Hofmann, E. Burcombe, J. Wei, R. Jiang, and Y. Chen. 2011. “Antibacterial Activity of Graphite, Graphite Oxide, Graphene Oxide, and Reduced Graphene Oxide: Membrane and Oxidative Stress.” ACS nano 5: 6971–6980.
   PubMed Web of Science ®Google Scholar
• Liu, W., Y. Wu, C. Wang, H. C. Li, T. Wang, C. Y. Liao, L. Cui, Q. F. Zhou, B. Yan, and G. B. Jiang. 2010. “Impact of Silver Nanoparticles on Human Cells: Effect of Particle Size.” Nanotoxicology 4: 319–330.
   PubMed Web of Science ®Google Scholar
• Lounis, N., C. Truffot-Pernot, J. Grosset, V. R. Gordeuk, and J. R. Boelaert. 2001. “Iron and Mycobacterium tuberculosis Infection.” Journal of clinical virology 20: 123–126.
   PubMed Web of Science ®Google Scholar
• Lowry, G. V., K. B. Gregory, S. C. Apte, and J. R. Lead. 2012. “Transformations of Nanomaterials in the Environment.” Environmental science & technology 46: 6893–6899.
   PubMed Web of Science ®Google Scholar
• Lundin, A. 1999. “Use of Firefly Luciferase in ATP-related Assays of Biomass, Enzymes, and Metabolites.” Methods in enzymology 305: 346–370.
   Web of Science ®Google Scholar
• Ma, C., Y. Rui, S. Liu, X. Li, B. Xing, and L. Liu. 2015. “Phytotoxic Mechanism of Nanoparticles: Destruction of Chloroplasts and Vascular Bundles and Alteration of Nutrient Absorption.” Scientific reports 5: 11618.
   PubMed Web of Science ®Google Scholar
• Mangadlao, J. D., C. M. Santos, M. J. L. Felipe, A. C. C. de Leon, D. F. Rodrigues, and R. C. Advincula. 2015. “On the Antibacterial Mechanism of Graphene Oxide (GO) Langmuir–Blodgett Films.” Chemical communications 51: 2886–2889.
   PubMed Web of Science ®Google Scholar
• Maurer, L. L., X. Yang, A. J. Schindler, R. K. Taggart, C. Jiang, H. Hsu-Kim, D. R. Sherwood, and J. N. Meyer. 2016. “Intracellular Trafficking Pathways in Silver Nanoparticle Uptake and Toxicity in Caenorhabditis elegans.” Nanotoxicology 10: 831–835.
   PubMed Web of Science ®Google Scholar
• Mueller, N. C., and B. Nowack. 2008. “Exposure Modeling of Engineered Nanoparticles in the Environment.” Environmental science & technology 42: 4447–4453.
   PubMed Web of Science ®Google Scholar
• Outten, C. E., and A. N. Albetel. 2013. “Iron Sensing and Regulation in Saccharomyces cerevisiae: Ironing Out the Mechanistic Details.” Current opinion in microbiology 16: 662–668.
   PubMed Web of Science ®Google Scholar
• Ozer, A., and R. K. Bruick. 2007. “Non-heme Dioxygenases: Cellular Sensors and Regulators Jelly Rolled into One?” Nature chemical biology 3: 144–153.
   PubMed Web of Science ®Google Scholar
• Perreault, F., A. F. De Faria, S. Nejati, and M. Elimelech. 2015. “Antimicrobial Properties of Graphene Oxide Nanosheets: Why Size Matters.” ACS nano 9: 7226–7236.
   PubMed Web of Science ®Google Scholar
• Pierik, A. J., D. J. A. Netz, and R. Lill. 2009. “Analysis of Iron-sulfur Protein Maturation in Eukaryotes.” Nature protocols 4: 753–766.
   PubMed Web of Science ®Google Scholar
• Puig, S., E. Askeland, and D. J. Thiele. 2005. “Coordinated Remodeling of Cellular Metabolism During Iron Deficiency Through Targeted mRNA Degradation.” Cell 120: 99–110.
   PubMed Web of Science ®Google Scholar
• Qu, G., S. Liu, S. Zhang, L. Wang, X. Wang, B. B. Sun, N. Y. Yin, et al. 2013. “Graphene Oxide Induces Toll-like Receptor 4 (TLR4)-dependent Necrosis in Macrophages.” ACS nano 7: 5732–5745.
   PubMed Web of Science ®Google Scholar
• Quilès, F., P. Polyakov, F. Humbert, and G. Francius. 2012. “Production of Extracellular Glycogen by Pseudomonas fluorescens: Spectroscopic Evidence and Conformational Analysis by Biomolecular Recognition.” Biomacromolecules 13: 2118–2127.
   PubMed Web of Science ®Google Scholar
• Ramanan, N., and Y. Wang. 2000. “A High-affinity Iron Permease Essential for Candida albicans Virulence.” Science (New York, N.Y.) 288: 1062–1064.
   PubMed Web of Science ®Google Scholar
• Regev-Rudzki, N., S. Karniely, N. N. Ben-Haim, and O. Pines. 2005. “Yeast Aconitase in Two Locations and Two Metabolic Pathways: Seeing Small Amounts is Believing.” Molecular biology of the cell 16: 4163–4171.
   PubMed Web of Science ®Google Scholar
• Ren, X., J. Li, X. Tan, W. Shi, C. Chen, D. Shao, T. Wen, et al. 2014. “Impact of Al2O3 on the Aggregation and Deposition of Graphene Oxide.” Environmental science & technology 48: 5493–5500.
   PubMed Web of Science ®Google Scholar
• Ren, X., Q. Wu, H. Xu, D. Shao, X. Tan, W. Shi, C. Chen, et al. 2016. “New insight into GO, Cadmium(II), Phosphate Interaction and its Role in GO Colloidal Behavior.” Environmental science & technology 50: 9361–9369.
   PubMed Web of Science ®Google Scholar
• Renton, F. J., and T. M. Jeitner. 1996. “Cell Cycle-dependent Inhibition of the Proliferation of Human Neural Tumor Cell Lines by Iron Chelators.” Biochemical pharmacology 51: 1553–1561.
   PubMed Web of Science ®Google Scholar
• Richardson, D. R., D. S. Kalinowski, S. Lau, P. J. Jansson, and D. B. Lovejoy. 2009. “Cancer Cell Iron Metabolism and the Development of Potent Iron Chelators as Anti-tumour Agents.” Biochimica et biophysica acta general subjects1790: 702–717.
   PubMed Web of Science ®Google Scholar
• Ruiz, O. N., K. S. Fernando, B. Wang, N. A. Brown, P. G. Luo, N. D. McNamara, and C. E. Bunker. 2011. “Graphene Oxide: A Nonspecific Enhancer of Cellular Growth.” ACS nano 5: 8100–8107.
   PubMed Web of Science ®Google Scholar
• Schmitt, M. P., and R. K. Holmes. 1991. “Iron-dependent Regulation of Diphtheria Toxin and Siderophore Expression by the Cloned Corynebacterium diphtheriae Repressor Gene dtxR in C. diphtheriae C7 Strains.” Infection & immunity 59: 1899–1904.
   PubMed Web of Science ®Google Scholar
• Seabra, A. B., A. J. Paula, R. de Lima, O. L. Alves, and N. Duran. 2014. “Nanotoxicity of Graphene and Graphene Oxide.” Chemical research in toxicology 27: 159–168.
   PubMed Web of Science ®Google Scholar
• Shakoury-Elizeh, M., O. Protchenko, A. Berger, J. Cox, K. Gable, T. M. Dunn, and C. C. Philpott. 2010. “Metabolic Response to Iron Deficiency in Saccharomyces cerevisiae.” The journal of biological chemistry 285: 14823–14833.
   PubMed Web of Science ®Google Scholar
• Shen, J., Y. Hu, M. Shi, X. Lu, C. Qin, C. Li, and M. Ye. 2009. “Fast and Facile Preparation of Graphene Oxide and Reduced Graphene Oxide Nanoplatelets.” Chemistry of materials 21: 3514–3520.
   Web of Science ®Google Scholar
• Shirzadegan, M., P. Christie, and J. R. Seemann. 1991. “An Efficient Method for Isolation of RNA from Tissue Cultured Plant Cells.” Nucleic acids research 19: 6055
   PubMed Web of Science ®Google Scholar
• Sitko, R., E. Turek, B. Zawisza, E. Malicka, E. Talik, J. Heimann, and R. Wrzalik. 2013. “Adsorption of Divalent Metal Ions from Aqueous Solutions Using Graphene Oxide.” Dalton transactions 42: 5682–5689.
   PubMed Web of Science ®Google Scholar
• Sun, Y., D. Shao, C. Chen, S. Yang, and X. Wang. 2013. “Highly Efficient Enrichment of Radionuclides on Graphene Oxide-supported Polyaniline.” Environmental science & technology 47: 9904–9910.
   PubMed Web of Science ®Google Scholar
• Tao, X., N. Schiering, H. Y. Zeng, D. Ringe, and J. R. Murphy. 1994. “Iron, DtxR, and the Regulation of Diphtheria Toxin Expression.” Molecular microbiology 14: 191–197.
   PubMed Web of Science ®Google Scholar
• Turco, R. F., M. Bischoff, Z. H. Tong, and L. Nies. 2011. “Environmental Implications of Nanomaterials: are We Studying the Right Thing?” Current opinion in biotechnology 22: 527–532.
   PubMed Web of Science ®Google Scholar
• Valles, C., C. Drummond, H. Saadaoui, C. A. Furtado, M. He, O. Roubeau, L. Ortolani, M. Monthioux, and A. Penicaud. 2008. “Solutions of Negatively Charged Graphene Sheets and Ribbons.” Journal of the american chemical society 130: 15802–15804.
   PubMed Web of Science ®Google Scholar
• Vasil, M. L., and U. A. Ochsner. 1999. “The Response of Pseudomonas aeruginosa to Iron: Genetics, Biochemistry and Virulence.” Molecular microbiology 34: 399–413.
   PubMed Web of Science ®Google Scholar
• Waltman, R. J., J. Pacansky, and C. W. Bates. 1993. “X-ray Photoelectron Spectroscopic Studies on Organic Photoconductors Evaluation of Atomic Charges on Chlorodiane Blue and p-(diethylamino) Benzaldehyde Diphenylhydrazone.” Chemistry of materials 5: 1799–1804.
   Web of Science ®Google Scholar
• Wang, J., and B. L. Chen. 2005. “Adsorption and Coadsorption of Organic Pollutants and a Heavy Metal by Graphene Oxide and Reduced Graphene Materials.” Chemical enginering journal 281: 379–388.
   Google Scholar
• Westerhoff, P., G. Song, K. Hristovski, and M. A. Kiser. 2011. “Occurrence and Removal of Titanium at Full Scale Wastewater Treatment Plants: Implications for TiO2 Nanomaterials.” Journal of environmental monitoring: JEM 13: 1195–1203.
   PubMed Web of Science ®Google Scholar
• Wu, X., S. Tan, Y. Xing, Q. Pu, M. Wu, and J. X. Zhao. 2017. “Graphene Oxide as an Efficient Antimicrobial Nanomaterial for Eradicating Multi-drug Resistant Bacteria In Vitro and In Vivo.” Colloid surface B 157: 1–9.
   PubMed Web of Science ®Google Scholar
• Xu, N., Y. Dong, X. Cheng, Q. Yu, K. Qian, J. Mao, B. Zhang, and M. Li. 2014. “Cellular Iron Homeostasis Mediated by the Mrs4-Ccc1-Smf3 Pathway is Essential for Mitochondrial Function, Morphogenesis and Virulence in Candida albicans.” BBA molecular cell research 1843: 629–639.
   PubMed Web of Science ®Google Scholar
• Zhao, G., J. Li, X. Ren, C. Chen, and X. Wang. 2011. “Few-layered Graphene Oxide Nanosheets as Superior Sorbents for Heavy Metal Ion Pollution Management.” Environmental science & technology 45: 10454–10462.
   PubMed Web of Science ®Google Scholar
• Zhu, Y., S. Murali, W. Cai, X. Li, J. W. Suk, J. R. Potts, and R. S. Ruoff. 2010. “Graphene and Graphene Oxide: Synthesis, Properties, and Applications.” Advanced materials (Deerfield Beach, Fla.) 22: 3906–3924.
   PubMed Web of Science ®Google Scholar
• Zou, X., L. Zhang, Z. Wang, and Y. Luo. 2016. “Mechanisms of the Antimicrobial Activities of graphene materials.” Journal of the american chemical society 138: 2064–2077.
   PubMed Web of Science ®Google Scholar