title: Lung distribution, quantification, co-localization and speciation of silver nanoparticles after lung exposure in mice.
abstract: Large knowledge gaps still exist on the toxicological mechanisms of silver (Ag) engineered nanoparticles (ENPs); a comprehensive understanding of the sources, biodistribution, toxicity and transformation of Ag ENPs along their life cycle and after transfer in living organisms is needed. In a previous study, mice were pulmonary exposed to Ag ENPs and local (lung) and systemic toxic effects together with biodistribution to organs including heart, liver, spleen and kidney were investigated. Here, Ag lung distribution, local concentration, co-localization with other elements such as Fe, Cu and S, and speciation were determined after lung exposure to Ag ENPs using micro X-ray fluorescence (μXRF), micro X-ray absorption near edge structure spectroscopy (μXANES) and micro proton-induced X-ray emission (μPIXE) techniques. We found that approximately a quarter of all macrophages in the lumen of the airways contained ENPs. High local concentrations of Ag were also detected in the lung tissue, probably phagocytized by macrophages. The largest part of the ENPs was dissolved and complexed to thiol-containing molecules. Increased concentrations of Fe and Cu observed in the Ag-rich spots suggest that these molecules are metallothioneins (MTs). These results give more insights on the behavior of Ag ENPs in the lung in vivo and will help in the understanding of the toxicological mechanisms of Ag ENPs.
authors.affiliation: Center for Environment and Health, KU Leuven, Leuven, Belgium. Electronic address: stijn.smulders@med.kuleuven.be.
authors.forename: Stijn
authors.initials: S
authors.lastname: Smulders
authors.affiliation: ISTerre, Université Grenoble Alpes, CNRS, F-38041 Grenoble, France. Electronic address: camille.Larue@ruhr-uni-bochum.de.
authors.forename: Camille
authors.initials: C
authors.lastname: Larue
authors.affiliation: ISTerre, Université Grenoble Alpes, CNRS, F-38041 Grenoble, France. Electronic address: geraldine.sarret@ujf-grenoble.fr.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Sarret
authors.affiliation: European Radiation Synchrotron Facility, Grenoble, France. Electronic address: hiram.castillo-michel@esrf.fr.
authors.forename: Hiram
authors.initials: H
authors.lastname: Castillo-Michel
authors.affiliation: Center for Environment and Health, KU Leuven, Leuven, Belgium. Electronic address: jeroen.vanoirbeek@med.kuleuven.be.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Vanoirbeek
authors.affiliation: Center for Environment and Health, KU Leuven, Leuven, Belgium. Electronic address: peter.hoet@med.kuleuven.be.
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019570:Inhalation Exposure / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010587:Phagocytosis; D012834:Silver / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D013052:Spectrometry, X-Ray Emission; D013499:Surface Properties; D014018:Tissue Distribution; D056928:X-Ray Absorption Spectroscopy
chemical_list: D012834:Silver
keywords: Micro X-ray absorption near edge structure spectroscopy (μXANES); Micro X-ray fluorescence (μXRF); Micro proton-induced X-ray emission (μPIXE); Nanoparticles; Silver