Reaction of human macrophages on protein corona covered TiO₂ nanoparticles

The cytokine secretion of primary cells of human macrophages during the interaction of TiO₂ nanoparticles (with an average primary size of 100-120nm) is investigated down to concentration levels suggested to be relevant for in vivo conditions. We find that high TiO₂ concentrations induce the cytokines Interleukin IL-1β, IL-6, and IL-10 secretion, while at low concentrations only IL-6 secretion is observed. To obtain further evidence on in vivo conditions we investigated the development and structure of the protein corona of the nanoparticles. We demonstrated that the surface of TiO₂ particles attract preferably secondary modified proteins which then induce cytokine secretion of macrophages. Our results indicate that concentration of corona covered TiO₂ particles below 1μg/ml induce IL-6 secretion which is reported to be responsible for the development of autoimmune diseases as well as for the secretion of acute phase proteins.