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Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation

Nature Nanotechnology volume 5, pages 354–359 (2010)Cite this article

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Abstract

We have shown previously that single-walled carbon nanotubes can be catalytically biodegraded over several weeks by the plant-derived enzyme, horseradish peroxidase1. However, whether peroxidase intermediates generated inside human cells or biofluids are involved in the biodegradation of carbon nanotubes has not been explored. Here, we show that hypochlorite and reactive radical intermediates of the human neutrophil enzyme myeloperoxidase catalyse the biodegradation of single-walled carbon nanotubes in vitro, in neutrophils and to a lesser degree in macrophages. Molecular modelling suggests that interactions of basic amino acids of the enzyme with the carboxyls on the carbon nanotubes position the nanotubes near the catalytic site. Importantly, the biodegraded nanotubes do not generate an inflammatory response when aspirated into the lungs of mice. Our findings suggest that the extent to which carbon nanotubes are biodegraded may be a major determinant of the scale and severity of the associated inflammatory responses in exposed individuals.

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Figure 1: Spectroscopic and electron microscopic evaluation of human myeloperoxidase (hMPO)-mediated degradation of nanotubes in vitro.
Figure 2: Molecular modelling, demonstrating possible nanotube interaction sites on hMPO.
Figure 3: IgG-functionalized nanotubes induce the release of hMPO and the generation of reactive oxygen species in human peripheral blood neutrophils.
Figure 4: Biodegradation of nanotubes in neutrophils evaluated by infrared and Raman spectroscopy.
Figure 5: Biodegraded nanotubes do not elicit a pro-inflammatory pulmonary response in C57BL/6 mice.

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Acknowledgements

This work was supported by grants from National Institute for Occupational Safety and Health (NIOSH) OH008282, National Institutes of Health HL70755, HL094488, U19AI068021, National Library of Medicine LM007994-05, National Occupational Research Agenda (NORA) 927000Y, 927Z1LU, Nanotechnology Research Center (NTRC) 927ZJHF, National Science Foundation (NSF) CAREER 0449117, Air Force Office of Scientific Research (AFOSR) FA9550-09-1-0478, 7th Framework Program of the European Commission (EC-FP7-NANOMMUNE-214281) and by the Science Foundation of Ireland, Strategic Research Cluster (SRC) BioNanointeract and Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Higher Education Authority (HEA) and Programme for Research in Third-Level Institutions (PRTLI). The authors would like to thank Marcel Bruchez for assistance with dynamic light scattering experiments.

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Authors and Affiliations

  1. Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Valerian E. Kagan, Nagarjun V. Konduru, Weihong Feng, Irina I. Vlasova, Natalia A. Belikova, Alexander Kapralov & Yulia Y. Tyurina

  2. Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Brett L. Allen, Pingping Gou & Alexander Star

  3. Department of Clinical Medicine and Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin, Ireland

    Jennifer Conroy & Yuri Volkov

  4. Department of Structural Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Naveena Yanamala & Judith Klein-Seetharaman

  5. Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Jingwen Shi & Bengt Fadeel

  6. Health Effects Laboratory Division (HELD), National Institute for Occupational Safety and Health (NIOSH) and Department of Physiology and Pharmacology, Pathology and Physiology Research Branch, West Virginia University, Morgantown, West Virginia, USA

    Elena R. Kisin, Ashley R. Murray & Anna A. Shvedova

  7. Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Jonathan Franks & Donna Stolz

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  1. Valerian E. Kagan
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Contributions

V.E.K., N.V.K., B.F. and A.S. designed the experiments, analysed the data and wrote the manuscript. W.F., J.S. and N.V.K. performed the neutrophil-based experiments. B.L.A. and N.V.K. participated in spectroscopic studies. I.I.V. and A.K. performed ESR measurements and gel electrophoresis. E.R.K., A.R.M. and A.S. designed and performed the animal experiments and evaluated the data. N.Y. and J.K.S. performed the molecular modelling studies. J.F. and D.S. carried out the electron microscopic studies. P.G. synthesized fluorescence labelled nanotubes. J.C. and Y.V. carried out the Raman microscopic studies. N.A.B. and Y.Y.T. performed the mass spectrometric analysis. All co-authors discussed the results and approved the final version of the manuscript.

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Correspondence to Valerian E. Kagan.

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Kagan, V., Konduru, N., Feng, W. et al. Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. Nature Nanotech 5, 354–359 (2010). https://doi.org/10.1038/nnano.2010.44

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