Variations in Biodistribution and Acute Response of Differently Shaped Titania Nanoparticles in Healthy Rodents

Abstract

Biodistribution; Nanotoxicity; Physico-chemical properties

Biodistribución; Nanotoxicidad; Propiedades fisicoquímicas

Biodistribució; Nanotoxicitat; Propietats fisicoquímiques

Titanium dioxide nanoparticles (TiO2 NPs) are one of the main sources of the nanoparticulate matter exposure to humans. Although several studies have demonstrated their potential toxic effects, the real nature of the correlation between NP properties and their interaction with biological targets is still far from being fully elucidated. Here, engineered TiO2 NPs with various geometries (bipyramids, plates, and rods) have been prepared, characterized and intravenously administered in healthy mice. Parameters such as biodistribution, accumulation, and toxicity have been assessed in the lungs and liver. Our data show that the organ accumulation of TiO2 NPs, measured by ICP-MS, is quite low, and this is only partially and transiently affected by the NP geometries. The long-lasting permanence is exclusively restricted to the lungs. Here, bipyramids and plates show a higher accumulation, and interestingly, rod-shaped NPs are the most toxic, leading to histopathological pulmonary alterations. In addition, they are also able to induce a transient increase in serum markers related to hepatocellular injury. These results indicate that rods, more than bipyramidal and spherical geometries, lead to a stronger and more severe biological effect. Overall, small physico-chemical differences can dramatically modify both accumulation and safety.

This research was funded by National Key Research and Development Program of China (No. 2017FYA0205301), Projects of International Cooperation and Exchanges NSFC (No. 82020108017), National Natural Science Foundation of China (No. 82272821); MCIN/AEI (PID2019-111218RB-I00 and RYC-2017-23457) and Centro Singular De Investigación de Galicia Accreditation 2019−2022, and ED431G 2019/03. Moreover, parts of this work were funded by the Cluster of Excellence ‘Advanced Imaging of Matter’ of the Deutsche Forschungsgemeinschaft (DFG)-EXC 2056-project ID 390715994; by Deutscher Akademischer Austauschdienst (DAAD); and by an Alexander von Humboldt fellowship. G.S. is supported by the Italian Association for Cancer Research (AIRC), grants 22820 and 22737. NGB and VP receive financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER, UE) proyectos de I + D + i de programación conjunta internacional MCIN/AEI (CONCORD, PCI2019-103436), co-funded by the European Union. P.B. is supported by the CONCORD project (EuroNanoMed III).