title: Novel lanthanide-labeled metal oxide nanoparticles improve the measurement of in vivo clearance and translocation.
abstract: The deposition, clearance and translocation of europium-doped gadolinium oxide nanoparticles in a mouse lung were investigated experimentally. Nanoparticles were synthesized by spray flame pyrolysis. The particle size, crystallinity and surface properties were characterized. Following instillation, the concentrations of particles in organs were determined with inductively coupled plasma mass spectrometry. The protein corona coating the nanoparticles was found to be similar to the coating on more environmentally relevant nanoparticles such as iron oxide. Measurements of the solubility of the nanoparticles in surrogates of biological fluids indicated very little propensity for dissolution, and the elemental ratio of particle constituents did not change, adding further support to the contention that intact nanoparticles were measured. The particles were intratracheally instilled into the mouse lung. After 24 hours, the target organs were harvested, acid digested and the nanoparticle mass in each organ was measured by inductively coupled plasma mass spectrometry (ICP-MS). The nanoparticles were detected in all the studied organs at low ppb levels; 59% of the particles remained in the lung. A significant amount of particles was also detected in the feces, suggesting fast clearance mechanisms. The nanoparticle system used in this work is highly suitable for quantitatively determining deposition, transport and clearance of nanoparticles from the lung, providing a quantified measure of delivered dose.
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Aamir D
authors.initials: AD
authors.lastname: Abid
authors.forename: Donald S
authors.initials: DS
authors.lastname: Anderson
authors.forename: Gautom K
authors.initials: GK
authors.lastname: Das
authors.forename: Laura S
authors.initials: LS
authors.lastname: Van Winkle
authors.forename: Ian M
authors.initials: IM
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D003460:Crystallization; D005063:Europium / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics*; D019570:Inhalation Exposure; D008168:Lung / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009928:Organ Specificity; D010316:Particle Size; D012995:Solubility; D013054:Spectrophotometry, Atomic; D013194:Staining and Labeling; D013499:Surface Properties; D014018:Tissue Distribution; D014961:X-Ray Diffraction
chemical_list: D005063:Europium; C030581:gadolinium oxide; D005682:Gadolinium