Nanoparticles can cause DNA damage across a cellular barrier

Gevdeep Bhabra1,10, Aman Sood1,10, Brenton Fisher1, Laura Cartwright2, Margaret Saunders2, William Howard Evans3, Annmarie Surprenant4, Gloria Lopez-Castejon4, Stephen Mann5, Sean A. Davis5, Lauren A. Hails5, Eileen Ingham6, Paul Verkade7, Jon Lane7, Kate Heesom8, Roger Newson9 & Charles Patrick Case1

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.

1. Bristol Implant Research Centre, Southmead Hospital, Bristol BS10 5NB, UK
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
3. Department of Medical Biochemistry and Immunology & Wales Heart Research Institute, Cardiff University, Cardiff CF14 4XN, Wales
4. Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
5. School of Chemistry, University of Bristol, Bristol BS8 1TS, UK
6. Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
7. Department of Biochemistry, University of Bristol, Bristol BS8 1TD, UK
8. School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK
9. Medical Statistics, National Heart and Lung Institute, Imperial College London SW7 2AZ, UK
10. These authors contributed equally to this work

Correspondence to: Charles Patrick Case1 e-mail: c.p.case@bristol.ac.uk

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