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 ¹⁹²Ir. 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, ¹⁹²Ir 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 ¹⁹²Ir 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.

Keywords::

• Aggregates
• carbon nanoparticle
• inhalation
• iridium nanoparticle
• rat lung
• secondary target organs
• translocation

Declaration of interest: This work was supported in part by EU FP6 PARTICLE_RISK 012912 (NEST) and by U.S. National Institutes of Health grant HL070542. The authors alone are responsible for the content and writing of the paper.