Survival mechanisms and xenobiotic susceptibility of keratinocytes exposed to metal-derived nanoparticles

Metal-derived nanoparticles (Mt-NPs) are increasingly used in cosmetology due to their ultraviolet shielding (titanium dioxide [TiO2]), antioxidant (cerium dioxide [CeO2]), and biocidal (silver [Ag]) properties. In the absence of overt toxicity (i.e. cell death), Mt-NPs are considered safe for cosmetic applications. However, there is little understanding about the mechanisms involved in the survival of keratinocytes exposed to subtoxic levels of Mt-NPs. Human keratinocytes (HaCaT) were exposed subacutely to subtoxic concentrations (≤30 μg/ml, 48-72 h) of rutile (r) TiO2 (cylindrical), CeO2 (cubic) and Ag (spherical) with a core / hydrodynamic size of 98% purity. Mt-NP uptake was indirectly quantified by changes in the light side scatter (SSC), where the kinetics (time/dose-response) suggested that the three types of Mt-NPs were similarly uptaken by keratinocytes. rTiO2 and CeO2, but not Ag-NPs, increased autophagy, whose inhibition prompted cell death. No increase in the steady-state le...