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

eng Science and Education Publishing American Journal of Nanomaterials 2372-3122 2015-11-03 3 2 40 56 10.12691/ajn-3-2-1 AJN2015321 article An integrated in Vitro and in Vivo Testing Approach to Assess Pulmonary Toxicity of Engineered Cadmium-Doped Silica Nanoparticles Uliana De Simone 1 Elisa Roda 1 Cinzia Signorini 2 Teresa Coccini teresa.coccini@fsm.it 3 Department of Clinical Surgical, Diagnostic and Pediatric Sciences, Faculty of Medicine and Surgery, University of Pavia, Pavia, Italy Department of Pathophysiology, Experimental Medicine, and Public Health, University of Siena, Siena, Italy Laboratory of Clinical and Experimental Toxicology, Toxicology Division, IRCCS Salvatore Maugeri Foundation, Scientific Institute of Pavia Medical Centre, Pavia, Italy 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 ̦g/ml, (ii) GSH depletion at 10̦g/ml, (iii) membrane alterations at 25 ̦g/ml, after 1-day, and (iv) cell growth and proliferation inhibition at 0.05 ̦g/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. http://pubs.sciepub.com/ajn/3/2/1/ajn-3-2-1.pdf pulmonary in vivo in vitro nanotoxicology silica cadmium