An integrated in Vitro and in Vivo Testing Approach to Assess Pulmonary Toxicity of Engineered Cadmium-Doped Silica Nanoparticles

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.