BIODISTRIBUTION AND IMPLICATIONS OF EXPOSURE TO GOLD NANOPARTICLES

Abstract

To examine biodistribution after exposure to 20-nm gold nanoparticles (AuNPs) and resultant impacts on organs with accumulated AuNPs, this work exposed rats to AuNPs through inhalation exposure and intravenous injection. Prior to exposure tests, synthesized AuNP solution underwent thorough characterization. Impurities were quantified; a newly identified non-AuNP component (acetate) enables completion of the stoichiometric equation of AuNP synthesis through the citrate reduction method. An optimal purification procedure was selected after systematic tests. A centrifugation operated at 7000 g for 20 min achieved satisfactory recovery of AuNPs and almost full removal of impurities. The treated AuNP solution remained stable for 20 days when it is stored in the dark at 4oC.

After 15-day exposure to airborne AuNPs of an original size of 20 nm, the lungs showed the highest accumulation of Au. Compared to 5-day exposure where Au was detected only in lung and olfactory bulb, the accumulation of Au in more than 20 organs at 15-day exposure demonstrates translocation of nanoparticles from the lungs to other organs. At similar doses of airborne AuNP in terms of number concentrations and agglomerated peak diameter aerosolized, inhaled AuNPs with an original size of 7-nm AuNPs distributed in 22 organs, more than that of 20-nm AuNPs (18 organs), particularly in more areas of the brain, including olfactory bulb, hippocampus, frontal cortex, straitum and cerebellum. The microarray analyses of the lungs and kidneys of rats exposed to airborne 20-nm AuNP showed changes in >30 genes (such as cytochrome c oxidase subunits, RT1 class II, locus Bb, myoglobin, thyroid hormone responsive protein, etc.). They are mainly related to functions of smooth muscles, antigen recognition, secretion and growth.

To compare with inhalation exposure and to address the potential impacts of introducing nanoparticles through intravenous injection, 20-nm AuNPs were injected once and the resultant biodistribution was examined at four time points, 1 day, 1 week, 1 month, and 2 months post injection. Injected AuNPs showed persistent accumulation of Au in liver and spleen. However, Au accumulation in the lungs decreased within 1 month. Significant accumulation of Au in kidney occurred when Au in feces and urine decreased. Coincident with the delayed accumulation in kidney, significant accumulation of Au in blood occurred two months post injection. Microarray results showed changes in >60 genes of liver and spleen related to detoxification, lipid metabolism, cell cycle, defense response, and circadian rhythm.

Differing from inhalation exposure, injected AuNPs exhibited increased accumulation of Au in liver, rapid clearance of Au in lung with non-detectable Au in brain, evidencing that exposure routes are important of determining the distribution and potential toxicity of AuNPs in the body.