Assessing the impact of the physical properties of industrially produced carbon nanotubes on their interaction with human primary macrophages in vitro
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Martin J.D. Clift
, Sabine Frey
Abstract
Currently it is not fully understood how carbon nanotubes (CNTs) may affect human health. Despite this, CNTs are produced at a tonne mass scale yearly. Due to their large production and intended use within a variety of applications it is imperative that a clear understanding of the hazard potential of CNTs is gained. The aim of this study therefore was to assess the impact of five different industrially produced CNTs which varied in their physical properties on the viability of human monocyte derived macrophages (MDM), and subsequently, at sub-lethal concentrations (0.005–0.02 mg/mL), their ability to cause oxidative stress and a pro-inflammatory response in these important immune cells over a 24-h period. None of the CNTs caused significant cytotoxicity up to 0.02 mg/mL after 24 h. Only the long multi-walled CNTs (MWNCTs) caused a significant, dose-dependent (0.005–0.02 mg/mL) reactive oxygen species production, whilst bundled MWCNTs showed a significant tumor necrosis factor alpha release after 24 h exposure at 0.02 mg/mL. No effects were observed for either tangled MWCNTs or short MWCNTs. It can be concluded from the findings of the present study that the industrially produced CNTs studied can cause hazardous effects in vitro that may be associated with their physical properties.
The authors would like to acknowledge the Adolphe Merkle Foundation, an Empa internal grant, as well as the Swiss National Science Foundation, the Swiss National research Programme 64 and the Swiss Nanoscience Institute (SNI) within the National Center of Research (NCCR) in Nanoscale Science for their financial support. The authors also thank Vicki Stone (Heriot-Watt University, Edinburgh, UK), Craig A. Poland (Institute of Occupational Medicine, Edinburgh, UK) Ken Donaldson and Rodger Duffin (Edinburgh University, UK) for their kind donation of the NTT, NTL and NTS samples.
Conflict of interest statement:
The authors declare no conflict of interest. The authors are entirely responsible for the data contained within and the writing of the manuscript.
References
1. Piccinno F, Gottschalk F, Seeger S, Nowack B. Industrial production quantities and uses of ten engineered nanomaterials in Europe and the world. J Nanopart Res 2012;14:1109.10.1007/s11051-012-1109-9Search in Google Scholar
2. Kostarelos K, Bianco A, Prato M. Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. Nat Nanotech 2009;4:627–33.10.1038/nnano.2009.241Search in Google Scholar
3. Robertson J. Realistic applications of CNTs. Mater Today 2004;7:46–52.10.1016/S1369-7021(04)00448-1Search in Google Scholar
4. NIOSH. General safe practices for working with engineered nanomaterials in research laboratories. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2012–147, 2012.Search in Google Scholar
5. Maynard AD, Baron PA, Foley M, Shvedova AA, Kisin ER, Castranova V. Exposure to carbon nanotube material: aerosol release during the handling of unrefined single-walled carbon nanotube material. J Tox Environ Health Part A 2004;67:87–107.10.1080/15287390490253688Search in Google Scholar PubMed
6. Mueller L, Gasser M, Raemy DO, Herzog F, Brandenberger C, Schmid O, et al. Realistic exposure methods for investigating the interaction of nanoparticles with the lung at the air-liquid interface in vitro. InSci J (Nanotech) 2011;1:30–64.10.5640/insc.010130Search in Google Scholar
7. Oberdorster G, Stone V, Donaldson K. Toxicology of nanoparticles: a historical perspective. Nanotox 2007;1:2–25.10.1080/17435390701314761Search in Google Scholar
8. Rothen-Rutishauser B, Blank F, Muehlfeld C, Gehr P. In vitro models of the human epithelial airway barrier to study the toxic potential of particulate matter. Exp Opin Drug Metab Toxicol 2008;4:1075–89.10.1517/17425255.4.8.1075Search in Google Scholar PubMed
9. Van Berlo D, Clift MJ, Albrecht C, Schins RP. Carbon nanotubes: an insight into the mechanisms of their potential genotoxicity. Swiss Med Wkly 2012;142:w13698.10.4414/smw.2012.13698Search in Google Scholar PubMed
10. Clift MJ, Foster EJ, Vanhecke D, Studer D, Wick P, Gehr P, et al. Investigating the interaction of cellulose nanofibers derived from cotton with a sophisticated 3D human lung cell coculture. Biomacromol 2011;12:3666–73.10.1021/bm200865jSearch in Google Scholar PubMed
11. Timbrell J. Principles of biochemical toxicology. CRC Press, UK: Taylor and Francis, 1999.Search in Google Scholar
12. Wick P, Clift MJ, Rosslein M, Rothen-Rutishauser B. A brief summary of the past 20 years of carbon nanotubes in science: a health and safety perspective. Chemsuschem 2011;4: 905–11.10.1002/cssc.201100161Search in Google Scholar PubMed
13. Johnston HJ, Hutchison GR, Christensen FM, Peters S, Hankin S, Aschberger K, et al. A critical review of the biological mechanisms underlying the in vivo and in vitro toxicity of carbon nanotubes: the contribution of physico-chemical characteristics. Nanotox 2010;4:207–46.10.3109/17435390903569639Search in Google Scholar PubMed
14. NIOSH Current Intelligence Bulletin 65. Occupational exposure to carbon nanotubes and nanofibres. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2013–145, 2013.Search in Google Scholar
15. Lam CW, James JT, McCluskey R, Hunter RL. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 2004;77:126–34.10.1093/toxsci/kfg243Search in Google Scholar PubMed
16. Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, et al. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 2005;289: L698–708.10.1152/ajplung.00084.2005Search in Google Scholar PubMed
17. Muller J, Huaux F, Moreau N, Misson P, Heilier JF, Delos M, et al. Respiratory toxicity of multiwall carbon nanotubes. Toxicol Appl Pharmacol 2005;207:221–31.10.1016/j.taap.2005.01.008Search in Google Scholar PubMed
18. Shvedova AA, Kisin E, Murray AR, Johnson VJ, Gorelik O, Arepalli S, et al. Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Am J Physiol Lung Cell Mol Physiol 2008;295:L552–65.10.1152/ajplung.90287.2008Search in Google Scholar PubMed PubMed Central
19. Ma-Hock L, Treumann S, Strauss V, Brill S, Luizi F, Mertler M, et al. Inhalation toxicity of multi-wall carbon nanotubes in rats exposed for 3 months. Toxicol Sci 2009;112:468–81.10.1093/toxsci/kfp146Search in Google Scholar PubMed
20. Pauluhn J. Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures. Toxicol Sci 2010;113:226–42.10.1093/toxsci/kfp247Search in Google Scholar PubMed
21. Porter DW, Hubbs AF, Mercer RR, Wu N, Wolfarth MG, Sriram K, et al. Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes. Toxicol 2010;269:136–47.10.1016/j.tox.2009.10.017Search in Google Scholar PubMed
22. Mercer RR, Hubbs AF, Scabilloni JF, Wang L, Battelli LA, Friend S, et al. Pulmonary fibrotic response to aspiration of multiwalled carbon nanotubes. Part Fibre Toxicol 2011;8:21.10.1186/1743-8977-8-21Search in Google Scholar PubMed PubMed Central
23. Stanton MF, Layard M, Tegeris A, Miller E, May M, Kent E. Carcinogenicity of fibrous glass: pleural response in the rat in relation to fiber dimension. J Nat Can Inst 1977;58:587–603.10.1093/jnci/58.3.587Search in Google Scholar PubMed
24. Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WA, Seaton A, et al. Carbon nanotubes introduced into the abdominal cavity ofmice show asbestoslike pathogenicity in a pilot study. Nat Nanotech 2008;3:423–8.10.1038/nnano.2008.111Search in Google Scholar PubMed
25. Donaldson K, Murphy FA, Duffin R, Poland CA. Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre tetention in the parietal pleura, inflammation and mesothelioma. Part Fibre Toxicol 2010;7:5.10.1186/1743-8977-7-5Search in Google Scholar PubMed PubMed Central
26. Murphy FA, Poland CA, Duffin R, Al-Jamal KT, Ali-Boucetta H, Nunes A, et al. Length-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleura. Am J Path 2011;178:6.10.1016/j.ajpath.2011.02.040Search in Google Scholar PubMed PubMed Central
27. Murphy FA, Schinwald A, Poland CA, Donaldson K. The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibers with macrophages stimulates them to amplify proinflammatory responses in mesothelial cells. Part Fibre Toxicol 2012;9:8.10.1186/1743-8977-9-8Search in Google Scholar PubMed PubMed Central
28. Fenoglio I, Greco G, Tomatis M, Muller J, Raymundo-PinÌfero E, Beguin Fo, et al. Structural defects play a major role in the acute lung toxicity of multiwall carbon nanotubes: physicochemical aspects. Chem Res Tox 2008;21:1690–7.10.1021/tx800100sSearch in Google Scholar PubMed
29. Muller J, Huaux Fo, Fonseca A, Nagy JB, Moreau N, Delos M, et al. Structural defects play a major role in the acute lung toxicity of multiwall carbon nanotubes: toxicological aspects. Chem Res Tox 2008;21:1698–705.10.1021/tx800101pSearch in Google Scholar PubMed
30. Tian F, Cui D, Schwarz H, Estrada GG, Kobayashi H. Cytotoxicity of single-wall carbon nanotubes on human fibroblasts. Toxicol In Vitro 2006;20:1202–12.10.1016/j.tiv.2006.03.008Search in Google Scholar PubMed
31. Stone V, Johnston H, Schins RP. Development of in vitro systems for nanotoxicology: methodological considerations. Crit Rev Toxicol 2009;39:613–26.10.1080/10408440903120975Search in Google Scholar PubMed
32. Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, et al. Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 2006;92:5–22.10.1093/toxsci/kfj130Search in Google Scholar PubMed
33. Wick P, Manser P, Limbach LK, Dettlaff-Weglikowska U, Krumeich F, Roth S, et al. The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Tox Letts 2007;168:121–31.10.1016/j.toxlet.2006.08.019Search in Google Scholar PubMed
34. Thurnherr T, Su DS, Diener L, Weinberg G, Manser P, Pfaender N, et al. Comprehensive evaluation of in vitro toxicity of three large-scale produced carbon nanotubes on human Jurkat T cells and a comparison to crocidolite asbestos. Nanotox 2009;3: 319–38.10.3109/17435390903276958Search in Google Scholar
35. Clift MJ, Rothen-Rutishauser B, Brown DM, Duffin R, Donaldson K, Proudfoot L, et al. The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line. Toxicol Appl Pharm 2008;232:418–27.10.1016/j.taap.2008.06.009Search in Google Scholar
36. Clift MJ, Gehr P, Rothen-Rutishauser B. In vitro testing for nanotoxicology: a valid alternative? Arch Toxicol 2011;85:723–31.10.1007/s00204-010-0560-6Search in Google Scholar
37. Clift MJ, Endes C, Vanhecke D, Wick P, Gehr P, Schins RP, et al. A comparative study of different in vitro lung cell culture systems to assess the most beneficial tool for screening the potential adverse effects of carbon nanotubes. Toxicol Sci (in Press).Search in Google Scholar
38. Donaldson K, Stone V, Borm PJ, Jimenez LA, Gilmour PS, Schins RP, et al. Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM10). Free Rad Biol Med 2003;34:1369–82.10.1016/S0891-5849(03)00150-3Search in Google Scholar
39. Brown DM, Kinloch IA, Bangert U, Windle AH, Walter DM, Walker GS, et al. An in vitro study of the potential of carbon nanotubes and nanofibres to induce inflammatory mediators and frustrated phagocytosis. Carbon 2007;45:1743–56.10.1016/j.carbon.2007.05.011Search in Google Scholar
40. Donaldson K, Tran CL. Inflammation caused by particles and fibers. Inhal Toxicol 2002;14:5–27.10.1080/089583701753338613Search in Google Scholar
41. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001;104:487–501.10.1016/S0092-8674(01)00237-9Search in Google Scholar
42. Kagan VE, Konduru NV, Feng W, Allen BL, Conroy J, Volkov Y, et al. Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. Nat. Nanotech 2010;5:354–9.Search in Google Scholar
43. Rothen-Rutishauser B, Brown DM, Piallier-Boyles M, Kinloch IA, Windle AH, Gehr P, et al. Relating the physicochemical characteristics and dispersion of multiwalled carbon nanotubes in different suspension media to their oxidative reacitivity in vitro and inflammation in vivo. Nanotox 2010;4:331–42.10.3109/17435390.2010.489161Search in Google Scholar PubMed
44. Bussy C, Pinault M, Cambedouzou J, Landry MJ, Jegou P, Mayne-L’hermite M, et al. Critical role of surface chemical modifications induced by length shortening on multi-walled carbon nanotubes-induced toxicity. Part Fibre Toxicol 2012;9:46.10.1186/1743-8977-9-46Search in Google Scholar PubMed PubMed Central
45. Thurnherr T, Brandenberger C, Fischer K, Diener L, Manser P, Maeder-Althaus X, et al. A comparison of acute and long-term effects of industrial multiwalled carbon nanotubes on human lung and immune cells in vitro. Tox Letts 2011;200:176–86.10.1016/j.toxlet.2010.11.012Search in Google Scholar PubMed
46. Lehmann A, Brandenberger C, Blank F, Gehr P, Rothen-Rutishauser B. A 3D model of the human epithelial airway barrier. In: Yarmush ML, Langer RS, editors. Alternatives to animal testing. Artech House 2010:239–60.Search in Google Scholar
47. Steiner S, Muller L, Popovicheva OB, Raemy DO, Czerwinski J, Comte P, et al. Cerium dioxide nanoparticles can interfere with the associated cellular mechanistic response to diesel exhaust exposure. Tox Letts 2012;214:218–25.10.1016/j.toxlet.2012.08.026Search in Google Scholar PubMed
48. Worle-Knirsch JM, Pulskamp K, Krug HF. Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Letts 2006;6:6.10.1021/nl060177cSearch in Google Scholar PubMed
49. Wilson MR, Lightbody JH, Donaldson K, Sales J, Stone V. Interactions between ultrafine particles and transition metals in vivo and in vitro. Toxciol Appl Pharm 2002;184:172–9.10.1006/taap.2002.9501Search in Google Scholar PubMed
50. Foucaud L, Wilson MR, Brown DM, Stone V. Measurement of reactive species production by nanoparticles prepared in biologically relevant media. Tox Letts 2007;174:1–9.10.1016/j.toxlet.2007.08.001Search in Google Scholar PubMed
51. Pal AK, Bello D, Budhlall B, Rogers E, Milton DK. Screening for oxidative stress elicited by engineered nanomaterials: evaluation of acellular DCFH Assay. Dose-Response 2012;10:308–30.10.2203/dose-response.10-036.PalSearch in Google Scholar PubMed PubMed Central
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Articles in the same Issue
- Masthead
- Masthead
- Editorial
- Milestones in Biomaterials Research: Special Issue on the occasion of the 20th anniversary of the German Society of Biomaterials
- Reviews
- Biomaterials – a history of 7000 years
- Biomaterials for enhancement of bone healing in osteoporotic fractures
- Surface functionalization of biomaterials with tissue-inductive artificial extracellular matrices
- Cell-material interaction
- Biological targeting with nanoparticles: state of the art
- Design and fabrication of scaffold-based tissue engineering
- Special Issue: Nanosafety (Part 2)
- Review
- The bio-nano-interface in predicting nanoparticle fate and behaviour in living organisms: towards grouping and categorising nanomaterials and ensuring nanosafety by design
- Highlights
- Antimicrobial efficacy, cytotoxicity, and ion release of mixed metal (Ag, Cu, Zn, Mg) nanoparticle polymer composite implant material
- Silver and carbon nanoparticles toxicity in sea urchin Paracentrotus lividus embryos
- Letter
- Assessing the impact of the physical properties of industrially produced carbon nanotubes on their interaction with human primary macrophages in vitro