Size-dependent clearance of gold nanoparticles from lungs of Sprague–Dawley rats after short-term inhalation exposure

Abstract

Gold nanoparticles are known to be distributed to many tissues following their oral, inhalation, or intravenous exposure. Information on the biodistribution and clearance of gold nanoparticles from these tissues is, therefore, important to understand their behavior in vivo. To study the effect of size on the biodistribution of gold nanoparticles, Sprague-Dawley rats were exposed by inhalation to small gold nanoparticles (13 nm in diameter on average) at an exposure concentration of 12.8 ± 2.42 µg/m(3), and to large gold nanoparticles (105 nm in diameter on average) at an exposure concentration of 13.7 ± 1.32 µg/m(3). The experimental animals were exposed to the gold nanoparticles and the control animals to fresh air for 5 days (6 h/day), followed by a recovery period of 1, 3, and 28 days in fresh air. None of the exposed animals exhibited any toxic response to the gold nanoparticles. Despite the difference in size, both small and large gold nanoparticles deposited mainly in rat lungs. Their biodistribution from the lungs to secondary target organs was significantly higher with the small compared to the large gold nanoparticles. While the large gold nanoparticles were only found in the blood, the small gold nanoparticles were detected in the liver, spleen, brain, testes, and blood. In addition, the elimination half-life of the small gold nanoparticles from the lungs was significantly shorter than that of the large gold nanoparticles. The present data may, therefore, suggest that the smaller gold nanoparticles are able to translocate from the lungs, the primary exposure organ to extrapulmonary organs at a faster rate than the larger gold nanoparticles and thus confirming previous observations reported in the literature.

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

“…This reinforces the suggestion that translocation and accumulation of NMs may be size-dependent with the smaller Au NMs more readily distributed to extra-pulmonary tissues than the larger NMs. The data from the study suggests possible clearance mechanisms for the materials over time -with the clearance via the reticuloendothelial system as highlighted by increasing levels of NMs in the spleen over time (Han et al 2014).…”

“…Several studies have noted that the pattern of distribution tends to be size and charge dependent (Hirn et al 2011) with markedly greater bio-distribution and accumulation of NMs in comparison to larger materials of the same chemical composition (Han et al 2014, Liu et al 2012b. Additionally, it has been suggested that smaller NMs can bind lung-lining layer proteins and use them as transporting vehicles across membranes, whereas micro-particles would be excluded from this transport mechanism (Lynch and Dawson 2008).…”

An assessment of applicability of existing approaches to predicting the bioaccumulation of conventional substances in nanomaterials

“…For example, a size-dependent bioaccumulation was demonstrated for AuNPs (5, 15, and 40 nm) in the Tellinid clam Scrobicularia plana (Pan et al 2012), in which a greater accumulation was confirmed for larger NPs. Similarly, longer half-lives (T 1/2 s) and mean residence times that may lead to greater bioaccumulation were observed for larger AuNPs than smaller AuNPs (Han et al 2015). Although a greater accumulation was also observed for larger bovine serum albuminstabilized 7.8-, 15-, and 46-nm AuNPs in filter-feeding bivalves (Corbicula fluminea; Hull et al 2011), a greater accumulation in the tilapia species Oreochromis niloticus was observed for smaller ZnONPs (10-30 nm) than for larger NPs (100 nm; Kaya et al 2015).…”

Differences in the toxicity of cerium dioxide nanomaterials after inhalation can be explained by lung deposition, animal species and nanoforms

“…Clearance of particles deposited in the lungs is known to depend mainly on the dose, size, shape and dissolution rate of primary particles and their aggregates and agglomerates (Greim and Ziegler-Skylakakis 2007;Keller et al 2014). Previous studies investigating the influence of particle size on the clearance have either found no influence of particle size on clearance (Semmler et al 2004;Buckley et al 2017) or a slower clearance of smaller particles (Geraets et al 2012;Keller et al 2014;Han et al 2015).…”