Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection

We investigated the effects of nSPs on the AD induced by intradermaly injected-mite antigen Dermatophagoides pteronyssinus (Dp) in NC/Nga mice. Ear thickness measurements and histopathological analysis revealed that a combined injection of amorphous silica particles (SPs) and Dp induced aggravation of AD in an SP size-dependent manner compared to that of Dp alone. In particular, aggravation was observed remarkably in nSP-injected groups. Furthermore, these effects were correlated with the excessive induction of total IgE and a stronger systemic Th2 response. We demonstrated that these results are associated with the induction of IL-18 and thymic stromal lymphopoietin (TSLP) in the skin lesions.A particle size reduction in silica particles enhanced IL-18 and TSLP production, which leads to systemic Th2 response and aggravation of AD-like skin lesions as induced by Dp antigen treatment. We believe that appropriate regulation of nanoparticle physicochemical properties, including sizes, is a critical determinant for the design of safer forms of NMs.With the development of nanotechnology, practical uses for nanomaterials (NMs) are rapidly spreading to a wide variety of fields, such as cosmetics, food, and medicine, because they have unique physicochemical properties and exert innovative functions [1-3]. These observations mean that intentional exposure of NMs is unavoidable in everyday life. However, it is a concern that NMs can exhibit unknown harmful effects [4,5]. For example, maternal exposure to titanium dioxide nanoparticles (nTiO2) induces gene expression alterations related to brain development [6]. We also revealed that amorphous silica nanoparticles (nSPs) and nTiO2 induce reproductive and/or liver toxicity compared with submicron-sized amorphous silica particles (SPs) [7,8]. However, little information exists on the potential hazard of NMs. To ensure the safety of NMs and enjoy their many benefits, it is essential to obtain more information on the relationship