A multidisciplinary and functional approach to neurotoxicity: the case of Quantum Dots

Nanosized materials are gaining a large interest in biomedical sciences for the wide range of possible applications, from diagnostic to therapeutic purposes. However, the assessment of biocompatibility and biosafety of nanoparticles (NPs) is a critical issue for further applications as diagnostic and imaging tools on humans. Among the NPs used for biomedical applications Quantum Dots (QDs) are of particular interest because of their properties as fluorescent semiconductor nanocrystals, which make them a promising tool for in vivo, in vitro and ex vivo imaging. The study described in this thesis focuses on long-term functional characterization of persistence in the organism of a single dose of non-modified QTracker® 800 QDs in a murine model. We recently reported that QDs accumulate in tissues and cross the BBB, remaining in the organs, including the brain for at least 3 weeks. Our purpose is to investigate persistence of QDs in the tissues and distribution pattern over time, along with possible pro-inflammatory effects of these NPs. Moreover, we were interesting in evaluating behavioural and electrophysiological parameters in order to identify possible secondary effects on the central nervous system (CNS). Lastly, we asked whether QDs were able to induce alterations in neuronal excitability in physiological and pathological conditions. Our data indicate that, 3 weeks after a single intravenous injection, QDs are still circulating in the bloodstream. Moreover, alterations in pro-inflammatory cytokines were found, in the liver and hippocampus. No alterations in behaviour and in the electroenphalographic rhythms of the QDs treated animals were identified. However, QDs seems to exacerbate the effect of unrelated inflammatory conditions and pro-convulsive agents in the brain. To conclude, the data presented in this thesis suggest that due to long term accumulation QDs may induce systemic inflammation, influencing neuronal excitability. Moreover, the results suggest that conventional in vivo tests used as first screening tools in toxicology, may not be enough to highlight NPs possible functional alterations involving the brain.