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Age-Dependent Rat Lung Deposition Patterns of Inhaled 20 Nanometer Gold Nanoparticles and their Quantitative Biokinetics in Adult Rats.

  • Kreyling WG Comprehensive Pneumology Center, Institute of Lung Biology and Disease , Helmholtz Zentrum München-German Research Center for Environmental Health , Ingolstaedter Landstrasse 1 , D-85764 Neuherberg/Munich , Germany.
  • Möller W Comprehensive Pneumology Center, Institute of Lung Biology and Disease , Helmholtz Zentrum München-German Research Center for Environmental Health , Ingolstaedter Landstrasse 1 , D-85764 Neuherberg/Munich , Germany.
  • Holzwarth U Directorate for Health, Consumers and Reference Materials , Joint Research Centre, European Commission , Via E. Fermi 2749 , I-21027 Ispra , Varese , Italy.
  • Hirn S Comprehensive Pneumology Center, Institute of Lung Biology and Disease , Helmholtz Zentrum München-German Research Center for Environmental Health , Ingolstaedter Landstrasse 1 , D-85764 Neuherberg/Munich , Germany.
  • Wenk A Comprehensive Pneumology Center, Institute of Lung Biology and Disease , Helmholtz Zentrum München-German Research Center for Environmental Health , Ingolstaedter Landstrasse 1 , D-85764 Neuherberg/Munich , Germany.
  • Schleh C Comprehensive Pneumology Center, Institute of Lung Biology and Disease , Helmholtz Zentrum München-German Research Center for Environmental Health , Ingolstaedter Landstrasse 1 , D-85764 Neuherberg/Munich , Germany.
  • Schäffler M Comprehensive Pneumology Center, Institute of Lung Biology and Disease , Helmholtz Zentrum München-German Research Center for Environmental Health , Ingolstaedter Landstrasse 1 , D-85764 Neuherberg/Munich , Germany.
  • Haberl N Comprehensive Pneumology Center, Institute of Lung Biology and Disease , Helmholtz Zentrum München-German Research Center for Environmental Health , Ingolstaedter Landstrasse 1 , D-85764 Neuherberg/Munich , Germany.
  • Gibson N Directorate for Health, Consumers and Reference Materials , Joint Research Centre, European Commission , Via E. Fermi 2749 , I-21027 Ispra , Varese , Italy.
  • Schittny JC Institute of Anatomy , University of Bern , Baltzerstrasse 2 , CH-3012 Berne , Switzerland.
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  • 2018-08-08
Published in:
  • ACS nano. - 2018
air−blood barrier translocation
alveolar macrophage
epithelial re-entrainment
extrapulmonary nanoparticle accumulation
gold nanoparticle aerosols
interstitial nanoparticle relocation
intratracheal inhalation
nanoparticle clearance
Administration, Inhalation
Age Factors
Animals
Female
Gold
Kinetics
Lung
Male
Metal Nanoparticles
Particle Size
Rats
Rats, Inbred WKY
Tissue Distribution
English The increasing use of gold nanoparticles leads to a possible increase of exposure by inhalation. Therefore, we have studied the deposition patterns of inhaled 20 nm gold nanoparticles (AuNP) in 7-90 day old rats and their biokinetics in 60 day old ones. Wistar-Kyoto rats inhaled intratracheally 20 nm 195Au-radiolabeled AuNP by negative pressure ventilation over 2 h. Immediately afterward lungs were excised, inflated and microwave dried. AuNP deposition was analyzed by single-photon emission computed tomography, computed-tomography and autoradiography. Completely balanced, quantitative biodistributions in major organs and all body tissues and total excretion were analyzed from 1 h to 28 d after inhalation. Intratracheal inhalation caused AuNP deposition predominately in the caudal lungs, independent of age. About 30% AuNP were deposited on airway epithelia and rapidly cleared by mucociliary clearance. About 80% of AuNP deposited in alveoli was relocated from the epithelium into the interstitium within 24 h and was inaccessible to broncho-alveolar lavage. During interstitial long-term retention, re-entrainment within macrophages back onto the lung epithelium and to the larynx and gastrointestinal tract (GIT) dominated AuNP clearance (rate 0.03 d-1) In contrast, AuNP-translocation across the air-blood barrier was much smaller leading to persistent retention in secondary organs and tissues in the ranking order liver > soft issue > spleen > kidneys > skeleton > blood > uterus > heart > brain. The age-independent, inhomogeneous AuNP deposition was probably caused by the negative pressure ventilation. Long-term AuNP clearance was dominated by macrophage-mediated transport from the interstitium to the larynx and GIT. Translocation across the rat air-blood barrier appeared to be similar to that of humans for similar sized AuNP.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/33689
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