BIODISTRIBUTION AND TOXICITY OF METALLIC NANOPARTICLES:IN VIVO STUDIES IN MICE

In the last decade, nanotechnology has emerged as one of the fastest growing area of science. This is a highly promising field for the generation of new engineering applications, consumer products, medical healthcare and medicine. However, the increasing development of nanomaterials (NMs) is not supported by in vivo studies taking systematically into consideration nanoparticles (NPs) types, doses and period of treatment that would allow to forecast possible adverse outcomes that might occur upon human exposure. In our studies, fully characterized silver nanoparticles (AgNPs) and iron oxide nanoparticles (IONP), designed for cancer treatment, were used to assess biodistribution and potential toxic effects after single intravenous and repeated oral administration in mice. Unexpected histopathological findings, strictly related to the physicochemical properties, i.e. size and vehicle used for the NPs synthesis, were observed after intravenous administration. This confirms that a complete characterization of NPs is of the most importance for the identification of in vivo outcomes. NPs mainly localized in organs containing large number of specialized tissue-resident macrophages belonging to the mononuclear phagocyte system. The retention of NPs in these tissues raises concerns about the potential toxicity. The 28 days repeated oral administration of AgNPs demonstrated that the brain is the organ where Ag accumulation takes place. In fact, Ag it is still detected in brain after the recovery period because of its low clearance. Morphological changes observed in the blood brain barrier (BBB), and the involvement of glial cells in response to AgNPs administration, suggested a perturbation of brain homeostasis that should be taken into consideration and further investigated.