pH-Dependent Toxicity of High Aspect Ratio ZnO Nanowires in Macrophages Due to Intracellular Dissolution

Handle URI:
http://hdl.handle.net/10754/599174
Title:
pH-Dependent Toxicity of High Aspect Ratio ZnO Nanowires in Macrophages Due to Intracellular Dissolution
Authors:
H. Müller, Karin; Kulkarni, Jaideep; Motskin, Michael; Goode, Angela; Winship, Peter; Skepper, Jeremy N.; Ryan, Mary P.; Porter, Alexandra E.
Abstract:
High-aspect ratio ZnO nanowires have become one of the most promising products in the nanosciences within the past few years with a multitude of applications at the interface of optics and electronics. The interaction of zinc with cells and organisms is complex, with both deficiency and excess causing severe effects. The emerging significance of zinc for many cellular processes makes it imperative to investigate the biological safety of ZnO nanowires in order to guarantee their safe economic exploitation. In this study, ZnO nanowires were found to be toxic to human monocyte macrophages (HMMs) at similar concentrations as ZnCl2. Confocal microscopy on live cells confirmed a rise in intracellular Zn2+ concentrations prior to cell death. In vitro, ZnO nanowires dissolved very rapidly in a simulated body fluid of lysosomal pH, whereas they were comparatively stable at extracellular pH. Bright-field transmission electron microscopy (TEM) showed a rapid macrophage uptake of ZnO nanowire aggregates by phagocytosis. Nanowire dissolution occurred within membrane-bound compartments, triggered by the acidic pH of the lysosomes. ZnO nanowire dissolution was confirmed by scanning electron microscopy/energy-dispersive X-ray spectrometry. Deposition of electron-dense material throughout the ZnO nanowire structures observed by TEM could indicate adsorption of cellular components onto the wires or localized zinc-induced protein precipitation. Our study demonstrates that ZnO nanowire toxicity in HMMs is due to pH-triggered, intracellular release of ionic Zn2+ rather than the high-aspect nature of the wires. Cell death had features of necrosis as well as apoptosis, with mitochondria displaying severe structural changes. The implications of these findings for the application of ZnO nanowires are discussed. © 2010 American Chemical Society.
Citation:
H. Müller K, Kulkarni J, Motskin M, Goode A, Winship P, et al. (2010) pH-Dependent Toxicity of High Aspect Ratio ZnO Nanowires in Macrophages Due to Intracellular Dissolution. ACS Nano 4: 6767–6779. Available: http://dx.doi.org/10.1021/nn101192z.
Publisher:
American Chemical Society (ACS)
Journal:
ACS Nano
Issue Date:
23-Nov-2010
DOI:
10.1021/nn101192z
PubMed ID:
20949917
Type:
Article
ISSN:
1936-0851; 1936-086X
Sponsors:
This project and K. Muller were funded by KAUST (King Abdullah University of Science and Technology)
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorH. Müller, Karinen
dc.contributor.authorKulkarni, Jaideepen
dc.contributor.authorMotskin, Michaelen
dc.contributor.authorGoode, Angelaen
dc.contributor.authorWinship, Peteren
dc.contributor.authorSkepper, Jeremy N.en
dc.contributor.authorRyan, Mary P.en
dc.contributor.authorPorter, Alexandra E.en
dc.date.accessioned2016-02-25T13:54:17Zen
dc.date.available2016-02-25T13:54:17Zen
dc.date.issued2010-11-23en
dc.identifier.citationH. Müller K, Kulkarni J, Motskin M, Goode A, Winship P, et al. (2010) pH-Dependent Toxicity of High Aspect Ratio ZnO Nanowires in Macrophages Due to Intracellular Dissolution. ACS Nano 4: 6767–6779. Available: http://dx.doi.org/10.1021/nn101192z.en
dc.identifier.issn1936-0851en
dc.identifier.issn1936-086Xen
dc.identifier.pmid20949917en
dc.identifier.doi10.1021/nn101192zen
dc.identifier.urihttp://hdl.handle.net/10754/599174en
dc.description.abstractHigh-aspect ratio ZnO nanowires have become one of the most promising products in the nanosciences within the past few years with a multitude of applications at the interface of optics and electronics. The interaction of zinc with cells and organisms is complex, with both deficiency and excess causing severe effects. The emerging significance of zinc for many cellular processes makes it imperative to investigate the biological safety of ZnO nanowires in order to guarantee their safe economic exploitation. In this study, ZnO nanowires were found to be toxic to human monocyte macrophages (HMMs) at similar concentrations as ZnCl2. Confocal microscopy on live cells confirmed a rise in intracellular Zn2+ concentrations prior to cell death. In vitro, ZnO nanowires dissolved very rapidly in a simulated body fluid of lysosomal pH, whereas they were comparatively stable at extracellular pH. Bright-field transmission electron microscopy (TEM) showed a rapid macrophage uptake of ZnO nanowire aggregates by phagocytosis. Nanowire dissolution occurred within membrane-bound compartments, triggered by the acidic pH of the lysosomes. ZnO nanowire dissolution was confirmed by scanning electron microscopy/energy-dispersive X-ray spectrometry. Deposition of electron-dense material throughout the ZnO nanowire structures observed by TEM could indicate adsorption of cellular components onto the wires or localized zinc-induced protein precipitation. Our study demonstrates that ZnO nanowire toxicity in HMMs is due to pH-triggered, intracellular release of ionic Zn2+ rather than the high-aspect nature of the wires. Cell death had features of necrosis as well as apoptosis, with mitochondria displaying severe structural changes. The implications of these findings for the application of ZnO nanowires are discussed. © 2010 American Chemical Society.en
dc.description.sponsorshipThis project and K. Muller were funded by KAUST (King Abdullah University of Science and Technology)en
dc.publisherAmerican Chemical Society (ACS)en
dc.subjectBiodegradationen
dc.subjectCytotoxicityen
dc.subjectDissolution morphologyen
dc.subjectElectron microscopyen
dc.subjectMacrophagesen
dc.subjectSimulated body fluiden
dc.subjectZinc oxide nanowiresen
dc.titlepH-Dependent Toxicity of High Aspect Ratio ZnO Nanowires in Macrophages Due to Intracellular Dissolutionen
dc.typeArticleen
dc.identifier.journalACS Nanoen
dc.contributor.institutionUniversity of Cambridge, Cambridge, United Kingdomen
dc.contributor.institutionImperial College London, London, United Kingdomen
dc.contributor.institutionMRC Human Nutrition Research, Cambridge, United Kingdomen

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