Nanoparticles can cause DNA damage across a cellular barrier.
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.
Bhabra
Gevdeep
G
Bristol Implant Research Centre, Southmead Hospital, Bristol, UK.
Sood
Aman
A
Fisher
Brenton
B
Cartwright
Laura
L
Saunders
Margaret
M
Evans
William Howard
WH
Surprenant
Annmarie
A
Lopez-Castejon
Gloria
G
Mann
Stephen
S
Davis
Sean A
SA
Hails
Lauren A
LA
Ingham
Eileen
E
Verkade
Paul
P
Lane
Jon
J
Heesom
Kate
K
Newson
Roger
R
Case
Charles Patrick
CP
D000255:Adenosine Triphosphate / Q000378:metabolism; D045744:Cell Line, Tumor; D002857:Chromium / Q000633:toxicity; D003035:Cobalt / Q000633:toxicity; D017630:Connexins / Q000378:metabolism; D004249:DNA Damage; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D053758:Nanoparticles / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D014168:Transferrin / Q000378:metabolism
D017630:Connexins; D014168:Transferrin; D002857:Chromium; D003035:Cobalt; D000255:Adenosine Triphosphate