Oxide Nanoparticle Uptake in Human Lung Fibroblasts:  Effects of Particle Size, Agglomeration, and Diffusion at Low Concentrations

Quantitative studies on the uptake of nanoparticles into biological systems should consider simultaneous agglomeration, sedimentation, and diffusion at physiologically relevant concentrations to assess the corresponding risks of nanomaterials to human health. In this paper, the transport and uptake of industrially important cerium oxide nanoparticles, into human lung fibroblasts is measured in vitro after exposing thoroughly characterized particle suspensions to a fibroblast cell culture for particles of four separate size fractions and concentrations ranging from 100 ng g(-1) to 100 microg g(-1) of fluid (100 ppb to 100 ppm). The unexpected findings at such low but physiologically relevant concentrations reveal a strong dependence of the amount of incorporated ceria on particle size, while nanoparticle number density or total particle surface area are of minor importance. These findings can be explained on the basis of a purely physical model. The rapid formation of agglomerates in the liquid is strongly favored for small particles due to a high number density while larger ones stay mainly unagglomerated. Diffusion (size fraction 25-50 nm) or sedimentation (size fraction 250-500 nm) limits the transport of nanoparticles to the fibroblast cells. The biological uptake processes on the surface of the cell are faster than the physical transport to the cell at such low concentrations. Comparison of the colloid stability of a series of oxide nanoparticles reveals that untreated oxide suspensions rapidly agglomerate in biological fluids and allows the conclusion thatthe presented transport and uptake kinetics at low concentrations may be extended to other industrially relevant materials.