The effect of primary particle size on biodistribution of inhaled gold nano-agglomerates.

Airborne engineered nanoparticles undergo agglomeration, and careful distinction must be made between primary and agglomerate size of particles, when assessing their health effects. This study compares the effects on rats undergoing 15-day inhalation exposure to airborne agglomerates of gold nanoparticles (AuNPs) of similar size distribution and number concentration (1 × 10(6) particles/cm(3)), but two different primary diameters of 7 nm or 20 nm. Inhalation of agglomerates containing 7-nm AuNPs resulted in highest deposition by mass concentration in the lungs, followed by brain regions including the olfactory bulb, hippocampus, striatum, frontal cortex, entorhinal cortex, septum, cerebellum; aorta, esophagus, and kidney. Eight organs/tissues especially the brain retained greater mass concentration of Au after inhalation exposure to agglomerates of 7-nm than 20-nm AuNPs. Macrophage mediated escalation followed by fecal excretion is the major pathway of clearing inhaled AuNPs in the lungs. Microarray analyses of the hippocampus showed mostly downregulated genes, related to the cytoskeleton and neurite outgrowth. Together, results in this study indicate disintegration of nanosized agglomerates after inhalation and show impact of primary size of particles on subsequent biodistribution.