Titanium dioxide aggregating nanoparticles induce autophagy and under-expression of microRNA 21 and 30a in A549 cell line: A comparative study with cobalt(II, III) oxide nanoparticles.

The toxicity of TiO nanoparticles (NPs) is controversial, while it is widely accepted for CoO NPs. We present a comparative study concerning the uptake of these NPs and their effect on cytoplasmic organelles and autophagy in a human lung carcinoma cell line (A549), including assays on the expression of autophagy-related microRNAs. The NP accumulation caused a fast dose- and time-dependent change of flow cytometry physical parameters particularly after TiO NP exposure. The intracellular levels of metals confirmed it, but the Co concentration was ten times higher than that of Ti. Both NPs caused neither necrosis nor apoptosis, but cytotoxicity was mainly evident for CoO NPs in the first 72h. TiO NPs caused autophagy, contrarily to CoO NPs. Furthermore, a significant and persistent downregulation of miRNA-21 and miRNA-30a was observed only in TiO NPs-treated cultures. The expression of miRNA-155 was similar for both NPs. Oxidative stress was evident only for CoO NPs, while both NPs perturbed endoplasmic reticulum and p-53 expression. In conclusion, the oxidative stress caused by CoO NPs can influence energy homeostasis and hamper the ability to detoxify and to repair the resulting damage, thus preventing the induction of autophagy, while TiO NPs elicit autophagy also under sub-toxic conditions.