| Summary: | <b>Background:</b> TiO<sub>2</sub> nanoparticles (TiO<sub>2</sub> NPs) are the nanomaterial most produced as an ultraviolet (UV) filter. However, TiO<sub>2</sub> is a semiconductor and, in nanoparticle size, is a strong photocatalyst, raising concerns about photomutagenesis. Mesoporous silica nanoparticles (MSN) were synthetized incorporating TiO<sub>2</sub> NPs (TiO<sub>2</sub>@MSN) to develop a cosmetic UV filter. The aim of this study was to assess the toxicity of TiO<sub>2</sub>@MSN, compared with bare MSN and commercial TiO<sub>2</sub> NPs, based on several biomarkers. <b>Materials and Methods:</b> Human peripheral blood mononuclear cells (PBMC) were exposed to TiO<sub>2</sub>@MSN, bare MSN (network) or commercial TiO<sub>2</sub> NPs for comparison. Exposed PBMC were characterized for cell viability/apoptosis, reactive oxygen species (ROS), nuclear morphology, and cytokines secretion. <b>Results:</b> All the nanoparticles induced apoptosis, but only TiO<sub>2</sub> NPs (alone or assembled into MSN) led to ROS and micronuclei. However, TiO<sub>2</sub>@MSN showed lower ROS and cytotoxicity with respect to the P25. Exposure to TiO<sub>2</sub>@MSN induced Th2-skewed and pro-fibrotic responses. <b>Conclusions:</b> Geno-cytotoxicity data indicate that TiO<sub>2</sub>@MSN are safer than P25 and MSN. Cytokine responses induced by TiO<sub>2</sub>@MSN are imputable to both the TiO<sub>2</sub> NPs and MSN, and, therefore, considered of low immunotoxicological relevance. This analytical assessment might provide hints for NPs modification and deep purification to reduce the risk of health effects in the settings of their large-scale manufacturing and everyday usage by consumers.
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