Skin Sensitization Potential of Sensitizers in the Presence of Metal Oxide Nanoparticles In Vitro

Silica (SiO2), titanium dioxide (TiO2), and zinc oxide (ZnO) nanoparticles (NPs) are widely used in dermal products. Their skin sensitization potential, especially their effects in combination with known sensitizers, is poorly studied in vitro and their sensitization inconsistently reported in animal studies. In this study, cellular assays were used to identify different steps of sensitization, the activation of keratinocytes and dendritic cells, when cells were exposed to these NPs in the absence and presence of sensitizers. Cellular systems included HaCaT keratinocytes and U937 (U-SENS (TM)) alone, as well as different co-culture systems of THP-1 cells with HaCaT cells (COCAT) and with primary keratinocytes. The effect of NPs differed between co-cultures and U-SENS (TM), whereas co-cultures with either primary keratinocytes or HaCaT cells responded similarly. Pre-exposure to ZnO NPs increased the U-SENS (TM) assay response to 2,4-dinitrochlorobenzene six-fold. The COCAT increase was maximally four-fold for the combination of SiO2 and trans cinnamaldehyde. When the THP-1 cells were separated from the keratinocytes by a membrane, the response of the co-culture system was more similar to U-SENS (TM). The direct contact with keratinocytes decreased the modulating effect of TiO2 and ZnO NPs but suggested an increase in response to sensitizers following dermal contact with SiO2 NPs.