NANOMEGA

Novel approach to toxicity testing of nanoparticles mimicing lung exposure. Possible protective effect of omega-3 acids

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 Obiettivo del progetto (Objective)

'As nanotechnology and materials science have progressed, large quantities of engineered nanoparticles (NPs) have been produced. NPs promise to revolutionize our lifestyles by improving many industrial and consumer products. However, there is considerable concern about their unknown impact on human health: with their unique physicochemical properties (size less than 100 nm), NPs differ from the corresponding bulk material. Here we address the urgent need to determine the potential effects of NPs on human health and environmental safety. Our objectives are: a) To develop and optimize a novel approach to in vitro NP testing using an epithelial cell culture model that mimics in vivo interactions of particles with cells; b) To study mechanisms of NP toxicity using cardiovascular/cardiopulmonary cell models to identify specific markers of oxidative stress and their role in activating signal pathways associated with the inflammatory response, DNA damage and repair; c) To investigate protection by omega-3 fatty acids against inflammatory effects of NPs, and possible modulation of DNA repair, in an in vitro model. This research will provide information on mechanisms of action of metal oxide NPs, and specifically on their effect on risk of cardiovascular/cardiopulmonary diseases. The results will contribute to protecting European public health, and will be crucially important for formulating policy on safety of nanotechnology. The ambitious research tasks provide an excellent opportunity for the career development of Dr. Rinna in this new field. By developing innovative techniques mimicking in vivo conditions, carrying out experiments on potential NP toxicity, and investigating how cells and DNA can be protected against injury, she will acquire an impressive range of expertise. By supervising master and co-supervising PhD students, she will improve her management and teaching skills and thus establish a base for a longer term position as a research team leader in Norway'

Introduzione (Teaser)

Information concerning the potential hazardous effects of manufactured nanoparticles on human health is urgently required. The fellow of the Intra-European Fellowships (IEF) examined how nutrition can protect against nanoparticle toxicity.

Descrizione progetto (Article)

Nanotechnology has rapidly entered our lives, promising to revolutionise health care and consumer products. The unique physicochemical properties of nanoparticles make them ideal for numerous applications.

Experimental evidence indicates that nanoparticles cause cytotoxicity, oxidative stress, genotoxicity and inflammatory responses, all of which could lead to cardiovascular diseases. However, no protective measures against nanoparticle-mediated injury have been proposed.

Seeking to address this, the EU-funded NANOMEGA project investigated the molecular mechanisms underlying silver nanoparticle and titanium dioxide toxicity. The focus of the study was on oxidative stress and its role in activating signal pathways associated with DNA damage and repair. In addition, the consortium explored the impact of nutrition and especially a diet rich in omega-3 fatty acids as a protective measure against nanoparticle toxicity.

NANOMEGA fellow observed that silver nanoparticles upregulated reactive oxygen species (ROS) within cells, a major contributor to oxidative stress. The capacity of nanoparticles to bind metals coupled to their surface chemistry could directly induce the formation of ROS. Alternatively, nanoparticles could be causing toxicity by interfering with the function of the ROS-producing NADPH-oxidases. With respect to DNA damage, experiments helped identify which molecules are central for repair following nanoparticle toxicity.

The key finding of the NANOMEGA study was the discovery that the addition of the DHA fatty acid significantly reduced nanoparticle-induced DNA damage. This was achieved by increasing the expression of DNA repair enzymes and hence improving the overall viability.

Taken together, NANOMEGA findings portray a picture of the toxicity mechanism caused by nanoparticles. Most importantly, for the first time interventions were proposed to minimise side-effects and nanotechnology safety has been improved.