TY - JOUR
T1 - Nanoparticles can cause DNA damage across a cellular barrier
AU - Bhabra, G
AU - Sood, Aman
AU - Fisher, B
AU - Cartwright, L
AU - Saunders, M.W
AU - Evans, W.H
AU - Surprenant, A
AU - Lopez-Castejon, G
AU - Mann, S
AU - Davis, S.A
AU - Hails, L.A
AU - Ingham, E
AU - Verkade, P
AU - Lane, J
AU - Heesom, K
AU - Newson, R
AU - Case, C.P
N1 - Other: Published on-line 5th November 2009
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-72549097805&partnerID=8YFLogxK
U2 - 10.1038/nnano.2009.313
DO - 10.1038/nnano.2009.313
M3 - Article (Academic Journal)
C2 - 19893513
SN - 1748-3387
VL - 4
SP - 876
EP - 883
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 12
ER -
