Uliana De Simone¹, Elisa Roda¹, Cinzia Signorini², Teresa Coccini^3,

An in vitro and in vivo testing strategy for assessing the pulmonary effects was used to investigate the safety characteristics of silica nanoparticles doped with cadmium (Cd-SiNPs). In A549 cells, Cd-SiNPs (0.5-100 μg/ml) caused (i) mitochondrial dysfunction and apoptosis at 1 μg/ml, (ii) GSH depletion at 10μg/ml, (iii) membrane alterations at 25 μg/ml, after 1-day, and (iv) cell growth and proliferation inhibition at 0.05 μg/ml after prolonged exposure. Cd-SiNP effects were more pronounced compared to CdCl₂. SiNPs affected GSH content only. In vivo results revealed early (1 day) and persistent (until 1 month) rat lung damage after intratracheal instillation of Cd-SiNPs (1mg/rat) in terms of enhanced apoptotic phenomena and altered lung parenchyma morphology. Cd-SiNPs and CdCl₂ caused a delayed occurrence of oxidative stress by increasing SOD1, iNOS, and F2-IsoPs. The latter was preceded by marked increase of F2-IsoPs levels in plasma. SiNPs did not cause oxidative stress. Cd-SiNPs showed a higher reactivity than CdCl₂ and SiNPs. In vitro and in vivo data on Cd-SiNP toxicity suggest that the lung is a susceptible target tissue. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological response to NPs.

pulmonary, in vivo, in vitro, nanotoxicology, silica, cadmium