Functional assessment of metal oxide nanoparticle toxicity in immune cells.
ABSTRACT Understanding the nanoparticle-cell interaction is critical for the safe development of nanomaterials. Herein, we explore the impact of three metal oxide nanoparticles, nonporous Stober SiO(2), mesoporous SiO(2), and nonporous anatase TiO(2) nanoparticles, on primary culture mast cells. Using transmission electron microscopy and inductively coupled plasma atomic emission spectroscopy, we demonstrate that each class of nanoparticle is internalized by the mast cells, localizing primarily in the secretory granules, with uptake efficiency increasing in the following order: nonporous SiO(2) < porous SiO(2) < nonporous TiO(2) nanoparticles. The influence of nanoparticle-laden granules was assessed using carbon-fiber microelectrode amperometry measurements that reveal functional changes in chemical messenger secretion from mast cell granules. Both nonporous and porous SiO(2) nanoparticles cause a decrease in the number of molecules released per granule, with nonporous SiO(2) also inducing a decrease in the amperometric spike frequency and, therefore, having a larger impact on cell function. As the two classes of SiO(2) nanoparticles vary only in their porosity, these results suggest that, while the mesoporous SiO(2) has a drastically larger total surface area due to the pores, the cell-contactable surface area, which is higher for the nonporous SiO(2), is more important in determining a nanoparticles' cellular impact. In comparison, exposure to nonporous TiO(2) slows the kinetics of secretion without altering the number of molecules released from the average granule. The varying immune cell response following exposure to nonporous SiO(2) and nonporous TiO(2) indicates that the nanoparticle-cell interactions are also modulated by surface chemistry.