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The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches.

Original publication

DOI

10.1038/nnano.2011.188

Type

Journal article

Journal

Nat Nanotechnol

Publication Date

06/11/2011

Volume

6

Pages

824 - 833

Keywords

Animals, Chromium Alloys, Connexins, Cornea, Cytokines, DNA Damage, Free Radicals, Humans, Lipid Bilayers, Metal Nanoparticles, Mice, Mice, Inbred C57BL, Mitochondria, Signal Transduction, Trophoblasts