Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs

Abstract

Currently, translocation of inhaled insoluble nanoparticles (NP) across membranes like the air-blood barrier into secondary target organs (STOs) is debated. Of key interest are the involved biological mechanisms and NP parameters that determine the efficiency of translocation. We performed NP inhalation studies with rats to derive quantitative biodistribution data on the translocation of NP from lungs to blood circulation and STOs. The inhaled NP were chain aggregates (and agglomerates) of either iridium or carbon, with primary particle sizes of 2-4 nm (Ir) and 5-10 nm (C) and aggregate sizes (mean mobility diameters) between 20 and 80 nm. The carbon aggregates contained a small fraction ( < 1%) of Ir primary particles. The insoluble aggregates were radiolabeled with (192)Ir. During 1 h of inhalation, rats were intubated and ventilated to avoid extrathoracic NP deposition and to optimize deep lung NP deposition. After 24 h, (192)Ir fractions in the range between 0.001 and 0.01 were found in liver, spleen, kidneys, heart, and brain, and an even higher fraction (between 0.01 and 0.05) in the remaining carcass consisting of soft tissue and bone. The fractions of (192)Ir carried with the carbon NP retained in STOs, the skeleton, and soft tissue were significantly lower than with NP made from pure Ir. Furthermore, there was significantly less translocation and accumulation with 80-nm than with 20-nm NP aggregates of Ir. These studies show that both NP characteristics--the material and the size of the chain-type aggregates--determine translocation and accumulation in STOs, skeleton, and soft tissue.

Gold nanostars for efficient in vitro and in vivo real-time SERS detection and drug delivery via plasmonic-tunable Raman/FTIR imaging

“…Kreyling et al also show that nanoparticles distribute into heart at the first blood circulation and start to aggregate into lung after 4 hours. 39 Our results also supports this idea that drugs are distributed in the blood, which is likely to provide greater access to well perfused organs such as the heart, liver and lung.…”

Outdoor air pollution and risk for kidney parenchyma cancer in 14 European cohorts

“…The airways are the primary target organs for inhaled particles but evidence from experimental studies with animals shows that ultrafine particles can translocate to other organs, such as the liver, kidneys, heart and brain 13,[31][32][33] . Although the amount of particles accumulating in secondary target organs, such as the kidney, is many times lower than the lung tissue dose, it may be relevant for carcinogenic processes 34,35 .…”

“…Most of the study areas were large cities and the surrounding suburban or rural communities, as specified in the online appendix (pp. [4][5][6][7][8][9][10][11][12][13]. A pooled analysis of all cohort data was not possible due to data-transfer and privacy issues but data from the four Stockholm cohorts (SNAC-K, SALT, 60-y/IMPROVE and SDPP) were pooled, and analysed and denoted as one Similarly, data from the two cohorts from the Netherlands (EPIC-MORGEN and EPIC-PROSPECT) were pooled, analysed and denoted as one [EPIC-NL].…”

“…Garcia-Perez et al found higher kidney cancer mortality in Spanish general populations exposed to ambient air pollution from incinerators and hazardous waste treatment plants 11 and a cohort study of a general Danish population found positive but statistically insignificant associations between nitrogen oxides (NO x ) at the residence and kidney cancer incidence but no association with amount of street traffic near the residence 12 . Further, ultrafine particles can translocate from the airways to the kidney and other organs of experimental animals 13 and experiments have shown that diesel particles can induce cancer-relevant processes in the kidneys 14,15 .…”

Human health hazards of persistent inorganic and carbon nanoparticles

“…There is some evidence that the pulmonary hazard of single-walled carbon nanotubes might be increased by the formation of nanotube assemblages in the lungs [60]. Kreyling et al [61] found that the translocation from the rat lung to the circulatory system and other organs of assemblages of Ir (2-4 nm) and C (5-10 nm) nanoparticles was reduced if compared with individual (monodisperse) Ir and C nanoparticles. Albanese and Chan [62] studying the uptake of monodisperse and assemblage of Au nanoparticles by mammalian cells, found the uptake to be dependent on cell type with aggregate uptakes of assemblages ranging from 25% lower to a twofold increase if compared with monodisperse nanoparticles.…”