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Toxicity of graphene oxide and multi-walled carbon nanotubes against human cells and zebrafish

Science China Chemistry volume 55, pages 2209–2216 (2012)Cite this article

Abstract

Graphene possesses unique physical and chemical properties, which have inspired a wide range of potential biomedical applications. However, little is known about the adverse effects of graphene on the human body and ecological environment. The purpose of our work is to make assessment on the toxicity of graphene oxide (GO) against human cell line (human bone marrow neuroblastoma cell line and human epithelial carcinoma cell line) and zebrafish (Danio rerio) by comparing the toxic effects of GO with its sister, multi-walled carbon nanotubes (MWNTs). The results show that GO has a moderate toxicity to organisms since it can induce minor (about 20%) cell growth inhibition and slight hatching delay of zebrafish embryos at a dosage of 50 mg/L, but did not result in significant increase of apoptosis in embryo, while MWNTs exhibit acute toxicity leading to a strong inhibition of cell proliferation and serious morphological defects in developing embryos even at relatively low concentration of 25 mg/L. The distinctive toxicity of GO and MWNTs should be ascribed to the different models of interaction between nanomaterials and organisms, which arises from the different geometric structures of nanomaterials. Collectively, our work suggests that GO does actual toxicity to organisms posing potential environmental risks and the result is also shedding light on the geometrical structure-dependent toxicity of graphitic nanomaterials.

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References

  1. Zerda ADL, Zavaleta C, Keren S, Vaithilingam S, Bodapati S, Liu Z, Levi J, Smith BR, Ma T-J, Oralkan O, Cheng Z, Chen X, Dai H, Khuri-Yakub BT, Gambhir SS. Carbon nanotubes as photoacoustic molecular imaging agents in living mice. Nat Biotech, 2008, 3: 557–562

    Google Scholar 

  2. Chen Z, Tabakman SM, Goodwin AP, Kattah MG, Daranciang D, Wang X, Zhang G, Li X, Liu Z, Utz PJ, Jiang K, Fan S, Dai H. Protein microarrays with carbon nanotubes as multicolor Raman labels. Nat Biotech, 2008, 26: 1285–1292

    Article  CAS  Google Scholar 

  3. Zhang L, Zhen SJ, Sang Y, Li JY, Wang Y, Zhan L, Peng L, Wang J, Li YF, Huang CZ. Controllable preparation of metal nanoparticle/carbon nanotube hybrids as efficient dark field light scattering agents for cell imaging. Chem Commun, 2010, 46: 4303–4305

    Article  CAS  Google Scholar 

  4. Liu Z, Fan AC, Rakhra K, Sherlock S, Goodwin A, Chen XY, Yang QW, Felsher DW, Dai HJ. Supramolecular stacking of doxorubicin on carbon nanotubes for in vivo cancer therapy. Angew Chem Int Ed, 2009, 48: 7668–7672

    Article  CAS  Google Scholar 

  5. Zhen SJ, Chen LQ, Xiao SJ, Li YF, Hu PP, Zhan L, Peng L, Song EQ, Huang CZ. Carbon nanotubes as a low background signal platform for a molecular aptamer beacon on the basis of long-range resonance energy transfer. Anal Chem, 2010, 82: 8432–8437

    Article  CAS  Google Scholar 

  6. Zhao YL, Xing GM, Chai ZF. Nanotoxicology: Are carbon nanotubes safe? Nat Nano, 2008, 3: 191–192

    Article  CAS  Google Scholar 

  7. Schipper ML, Nakayama-Ratchford N, Davis CR, Kam NWS, Chu P, Liu Z, Sun X, Dai H, Gambhir SS. A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice. Nat Nano, 2008, 3: 216–221

    Article  CAS  Google Scholar 

  8. Jia G, Wang HF, Yan L, Wang X, Pei RJ, Yan T, Zhao YL, Guo XB. Cytotoxicity of carbon nanomaterials: Single-wall nanotube, multi-wall nanotube, and fullerene. Environ Sci Technol, 2005, 39: 1378–1383

    Article  CAS  Google Scholar 

  9. Geim AK. Graphene: Status and prospects. Science, 2009, 324: 1530–1534

    Article  CAS  Google Scholar 

  10. Li XL, Wang XR, Zhang L, Lee SW, Dai HJ. Chemically derived, ultrasmooth graphene nanoribbon semiconductors. Science, 2008, 319: 1229–1232

    Article  CAS  Google Scholar 

  11. Jiang Z, Henriksen EA, Tung LC, Wang YJ, Schwartz ME, Han MY, Kim P, Stormer HL. Infrared spectroscopy of Landau levels of graphene. Phys Rev Lett, 2007, 98

  12. Yang K, Zhang SA, Zhang GX, Sun XM, Lee ST, Liu ZA. Graphene in mice: Ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett, 2010, 10: 3318–3323

    Article  CAS  Google Scholar 

  13. Castro Neto AH, Guinea F, Peres NMR, Novoselov KS, Geim AK. The electronic properties of graphene. Rev Modern Phys, 2009, 81: 109–162

    Article  CAS  Google Scholar 

  14. Li N, Zhang X, Song Q, Su R, Zhang Q, Kong T, Liu L, Jin G, Tang M, Cheng G. The promotion of neurite sprouting and outgrowth of mouse hippocampal cells in culture by graphene substrates. Biomaterials, 2011, 32: 9374–9382

    Article  CAS  Google Scholar 

  15. Liu Z, Robinson JT, Sun X, Dai H. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J Am Chem Soc, 2008, 130: 10876–10877

    Article  CAS  Google Scholar 

  16. Yang K, Wan J, Zhang S, Zhang Y, Lee S-T, Liu Z. In vivo pharmacokinetics, long-term biodistribution, and toxicology of PEGylated graphene in mice. Acs Nano, 2010, 5: 516–522

    Article  CAS  Google Scholar 

  17. Chang Y, Yang ST, Liu JH, Dong E, Wang Y, Cao A, Liu Y, Wang H. In vitro toxicity evaluation of graphene oxide on A549 cells. Toxicol Lett, 2011, 200: 201–210

    Article  CAS  Google Scholar 

  18. Wang K, Ruan J, Song H, Zhang J, Wo Y, Guo S, Cui D. Biocompatibility of graphene oxide. Nanoscale Res Lett, 2011, 6: 1–8

    Google Scholar 

  19. Zhang YB, Ali SF, Dervishi E, Xu Y, Li ZR, Casciano D, Biris AS. Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. Acs Nano, 2010, 4: 3181–3186

    Article  CAS  Google Scholar 

  20. Hu W, Peng C, Lv M, Li X, Zhang Y, Chen N, Fan C, Huang Q. Protein corona-mediated mitigation of cytotoxicity of graphene oxide. Acs Nano, 2011, 5: 3693–3700

    Article  CAS  Google Scholar 

  21. Liao KH, Lin YS, Macosko CW, Haynes CL. Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts. Acs Appl Mater Interface, 2011, 3: 2607–2615

    Article  CAS  Google Scholar 

  22. Akhavan O, Ghaderi E. Toxicity of graphene and graphene oxide nanowalls against bacteria. Acs Nano, 2010, 4: 5731–5737

    Article  CAS  Google Scholar 

  23. Hu W, Peng C, Luo W, Lv M, Li X, Li D, Huang Q, Fan C. Graphene-based antibacterial paper. Acs Nano, 2010, 4: 4317–4323

    Article  CAS  Google Scholar 

  24. Liu S, Zeng TH, Hofmann M, Burcombe E, Wei J, Jiang R, Kong J, Chen Y. Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress. Acs Nano, 2011, 5: 6971–6980

    Article  CAS  Google Scholar 

  25. Sanchez VC, Jachak A, Hurt RH, Kane AB. Biological interactions of graphene-family nanomaterials: an interdisciplinary review. Chem. Res Toxicol, 2012, 25: 15–34

    Article  CAS  Google Scholar 

  26. Zhang L, Huang CZ, Li YF, Xiao SJ, Xie JP. Label-free detection of sequence-specific DNA with multiwalled carbon nanotubes and their light scattering signals. J Phys Chem B, 2008, 112: 7120–7122

    Article  CAS  Google Scholar 

  27. Hu P, Huang CZ, Li YF, Ling J, Liu YL, Fei LR, Xie JP. Magnetic particle-based sandwich sensor with DNA-modified carbon nanotubes as recognition elements for detection of DNA hybridization. Anal Chem, 2008, 80: 1819–1823

    Article  CAS  Google Scholar 

  28. Park S, Ruoff RS. Chemical methods for the production of graphenes. Nat Nano, 2009, 4: 217–224

    Article  CAS  Google Scholar 

  29. Chen LQ, Xiao SJ, Peng L, Wu T, Ling J, Li YF, Huang CZ. Aptamer-based silver nanoparticles used for intracellular protein imaging and single nanoparticle spectral analysis. J Phys Chem B, 2010, 114: 3655–3659

    Article  CAS  Google Scholar 

  30. Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. Stages of embryonic development of the zebrafish. Dev Dynam, 1995, 203: 253–310

    Article  CAS  Google Scholar 

  31. Usenko CY, Harper SL, Tanguay RL. In vivo evaluation of carbon fullerene toxicity using embryonic zebrafish. Carbon, 2007, 45: 1891–1898

    Article  CAS  Google Scholar 

  32. Welsher K, Liu Z, Daranciang D, Dai H. Selective probing and imaging of cells with single walled carbon nanotubes as near-Infrared fluorescent molecules. Nano Lett, 2008, 8: 586–590

    Article  CAS  Google Scholar 

  33. Brunner TJ, Wick P, Manser P, Spohn P, Grass RN, Limbach LK, Bruinink A, Stark WJ. In vitro cytotoxicity of oxide nanoparticles: Comparison to asbestos, silica, and the effect of particle solubility. Environ Sci Technol, 2006, 40: 4374–4381

    Article  CAS  Google Scholar 

  34. Fako VE, Furgeson DY. Zebrafish as a correlative and predictive model for assessing biomaterial nanotoxicity. Adv Drug Del Rev, 2009, 61: 478–486

    Article  CAS  Google Scholar 

  35. Cheng JP, Flahaut E, Cheng SH. Effect of carbon nanotubes on developing zebrafish (Danio rerio) embryos. Environ Toxicol Chem, 2007, 26: 708–716

    Article  CAS  Google Scholar 

  36. Hallare AV, Köhler HR, Triebskorn R. Developmental toxicity and stress protein responses in zebrafish embryos after exposure to diclofenac and its solvent, DMSO. Chemosphere, 2004, 56: 659–666

    Article  CAS  Google Scholar 

  37. Chen X, Tam UC, Lee GS, Rabuka D, Zettl A, Bertozzi CR. Interfacing carbon nanotubes with living cells. J Am Chem Soc, 2006, 128: 6292–6293

    Article  CAS  Google Scholar 

  38. Liu XY, Vinson D, Abt D, Hurt RH, Rand DM. Differential toxicity of carbon nanomaterials in drosophila: Larval dietary uptake Is benign, but adult exposure causes locomotor impairment and mortality. Environ Sci Technol, 2009, 43: 6357–6363

    Article  CAS  Google Scholar 

  39. Pyati UJ, Look AT, Hammerschmidt M. Zebrafish as a powerful vertebrate model system for in vivo studies of cell death. Semin Cancer Biol, 2007, 17: 154–165

    Article  CAS  Google Scholar 

  40. Liu B, Li X, Li B, Xu B, Zhao Y. Carbon nanotube based artificial water channel protein: Membrane perturbation and water transportation. Nano Lett, 2009, 9: 1386–1394

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Ministry Key Laboratory on Luminescence and Real-Time Analysis; College of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China

    LiQiang Chen, PingPing Hu, Li Zhang & ChengZhi Huang

  2. Yunnan Key Laboratory of International Rivers and Transboundary Eco-Security, Asian International Rivers Center, Yunnan University, Kunming, 650091, China

    LiQiang Chen

  3. School of Life Sciences, Southwest University, Chongqing, 400715, China

    PingPing Hu, SiZhou Huang & LingFei Luo

  4. College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China

    ChengZhi Huang

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  1. LiQiang Chen
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  2. PingPing Hu
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Correspondence to ChengZhi Huang.

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Chen, L., Hu, P., Zhang, L. et al. Toxicity of graphene oxide and multi-walled carbon nanotubes against human cells and zebrafish. Sci. China Chem. 55, 2209–2216 (2012). https://doi.org/10.1007/s11426-012-4620-z

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  • DOI: https://doi.org/10.1007/s11426-012-4620-z

Keywords

  • graphene oxide
  • multi-walled carbon nanotubes
  • toxicity
  • cellular apoptosis
  • zebrafish