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Abstract

The increasing use of nanoparticles in medicine has raised concerns over their ability to gain access to privileged sites in the body. Here, we show that cobalt–chromium nanoparticles (29.5 ± 6.3 nm in diameter) can damage human fibroblast cells across an intact cellular barrier without having to cross the barrier. The damage is mediated by a novel mechanism involving transmission of purine nucleotides (such as ATP) and intercellular signalling within the barrier through connexin gap junctions or hemichannels and pannexin channels. The outcome, which includes DNA damage without significant cell death, is different from that observed in cells subjected to direct exposure to nanoparticles. Our results suggest the importance of indirect effects when evaluating the safety of nanoparticles. The potential damage to tissues located behind cellular barriers needs to be considered when using nanoparticles for targeting diseased states.

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Acknowledgements

Advice and discussion was kindly provided by A. Poole and A. Halestrap (University of Bristol). Support from the Research Foundation Non-medical Committee of the charitable trusts for the University Hospitals Bristol is acknowledged.

Author information

Author notes

    • Gevdeep Bhabra
    •  & Aman Sood

    These authors contributed equally to this work

Affiliations

  1. Bristol Implant Research Centre, Southmead Hospital, Bristol BS10 5NB, UK

    • Gevdeep Bhabra
    • , Aman Sood
    • , Brenton Fisher
    •  & Charles Patrick Case
  2. Biophysics Research Unit, Department of Medical Physics & Bioengineering, Bristol Haematology & Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Horfield Road, Bristol BS2 8ED, UK

    • Laura Cartwright
    •  & Margaret Saunders
  3. Department of Medical Biochemistry and Immunology & Wales Heart Research Institute, Cardiff University, Cardiff CF14 4XN, Wales

    • William Howard Evans
  4. Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK

    • Annmarie Surprenant
    •  & Gloria Lopez-Castejon
  5. School of Chemistry, University of Bristol, Bristol BS8 1TS, UK

    • Stephen Mann
    • , Sean A. Davis
    •  & Lauren A. Hails
  6. Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK

    • Eileen Ingham
  7. Department of Biochemistry, University of Bristol, Bristol BS8 1TD, UK

    • Paul Verkade
    •  & Jon Lane
  8. School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK

    • Kate Heesom
  9. Medical Statistics, National Heart and Lung Institute, Imperial College London SW7 2AZ, UK

    • Roger Newson

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Contributions

C.P.C., G.B., A.S., M.S. and L.C. conceived and designed the experiments. G.B., A.S., L.C., B.F., G.L., S.D., L.H., P.V., J.L. and K.H. performed the experiments. C.P.C., G.B., A.S., L.C., M.S., W.H.E., A.-M.S., G.L., S.D., L.H., P.V., J.L. and K.H. analysed the data. M.S., W.H.E., A.M.S. and E.I. contributed materials and analysis tools. C.P.C., G.B., A.S., W.H.E. and S.M. co-wrote the paper.

Corresponding author

Correspondence to Charles Patrick Case.

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DOI

https://doi.org/10.1038/nnano.2009.313

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