NanoLegaTox: When old meets new: A novelty study on the human uptake, genotoxicity and immunotoxicity of nanoparticles and legacy contaminants mixtures (POCI-01-0145-FEDER-029651)
ISPUP; CIIMAR - Interdisciplinary Centre of Marine and Environmental Research; CICECO - Aveiro Institute of Materials
Nanotoxicity assessments usually focus on single nanoparticle effects, overlooking interactions with other contaminants. In the environment, nanoparticles are expected to co-exist with other toxic species, such as metal(oids). It is also expected that these interactions will affect their behaviour, uptake and toxicity. The aim of project NanoLegaTox is to explore the toxicological effects on human lungs, brain and liver of titanium dioxide and cerium oxide nanoparticles, when in presence of arsenic and mercury, two of the most toxic and persistent metals present in the environment.
Other goals include:
i) Understand the contaminants-cell/organ interaction and induced toxicity;
ii) Assess the changes in nanoparticles’ physicochemical characteristics upon exposure to other chemical contaminants and determine how this affects their toxicity and interaction with the cell;
iii) Establish in vitro and in vivo acute and chronic toxicity of multi-contaminant solutions to lungs, brain and liver, at environmental realistic concentrations;
iv) Compare the uptake of the contaminants when alone versus co-exposure on different cells/organs.
In vitro studies will be performed on cell lines representative of organs proven to undergo toxic effects when exposed to these contaminants: lungs (A549), brain (SH-SY5Y) and liver (HepG2). In vivo studies will be performed on zebrafish and serve the purpose of correlating its findings with the ones from in vitro experiments and attempt to compare toxicity at cell and organism levels. Relevant endpoints of cell viability, genotoxicity, oxidative stress, epigeneticityand immunogenicity will be analysed using state-of-the-art techniques. Detailed characterization of NPs in all stages of the study (previous, during and after exposure) is key to the project and includes particle size distribution, shape, agglomeration/aggregation state, surface area, zeta potential, surface and elemental composition, TEM and SEM. The project will also validate procedures to be used in future assessments and other investigators. Ultimately, this work intends to provide a novel and multidisciplinary view over the toxicity of nanoparticles in the presence of legacy contaminants, uniting the areas of nanotechnology, toxicology and analytical chemistry. The outcomes will support the sustainable growth of nanotechnology and the development of safer NPs (safe-by-design), meeting the National and Regional Strategies for Smart Specialisation in the areas of health, environment and materials. The strength of this project lies on its novelty, recognized need and multidisciplinarity and on the expertise of researchers from the three scientific fields needed for the execution of the work plan (toxicology, nanotechnology, and environmental analytical chemistry), and the renowned institutions involved (ISPUP; CICECO; CIIMAR) that ensure the availability of all required equipment and techniques.