title: Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Inhalative nanocarriers for local or systemic therapy are promising. Gold nanoparticles (AuNP) have been widely considered as candidate material. Knowledge about their interaction with the lungs is required, foremost their uptake by surface macrophages and epithelial cells.
  
  
  METHODS
  Scnn1b-Tg and Wt mice inhaled a 21-nm AuNP aerosol for 2 h. Immediately (0 h) or 24 h thereafter, bronchoalveolar lavage (BAL) macrophages and whole lungs were prepared for stereological analysis of AuNP by electron microscopy.
  
  
  RESULTS
  AuNP were mainly found as singlets or small agglomerates of ≤ 100 nm diameter, at the epithelial surface and within lung-surface structures. Macrophages contained also large AuNP agglomerates (> 100 nm). At 0 h after aerosol inhalation, 69.2±4.9% AuNP were luminal, i.e. attached to the epithelial surface and 24.0±5.9% in macrophages in Scnn1b-Tg mice. In Wt mice, 35.3±32.2% AuNP were on the epithelium and 58.3±41.4% in macrophages. The percentage of luminal AuNP decreased from 0 h to 24 h in both groups. At 24 h, 15.5±4.8% AuNP were luminal, 21.4±14.2% within epithelial cells and 63.0±18.9% in macrophages in Scnn1b-Tg mice. In Wt mice, 9.5±5.0% AuNP were luminal, 2.2±1.6% within epithelial cells and 82.8±0.2% in macrophages. BAL-macrophage analysis revealed enhanced AuNP uptake in Wt animals at 0 h and in Scnn1b-Tg mice at 24 h, confirming less efficient macrophage uptake and delayed clearance of AuNP in Scnn1b-Tg mice.
  
  
  CONCLUSIONS
  Inhaled AuNP rapidly bound to the alveolar epithelium in both Wt and Scnn1b-Tg mice. Scnn1b-Tg mice showed less efficient AuNP uptake by surface macrophages and concomitant higher particle internalization by alveolar type I epithelial cells compared to Wt mice. This likely promotes AuNP depth translocation in Scnn1b-Tg mice, including enhanced epithelial targeting. These results suggest AuNP nanocarrier delivery as successful strategy for therapeutic targeting of alveolar epithelial cells and macrophages in COPD.
authors.forename: Marianne
authors.initials: M
authors.lastname: Geiser
authors.forename: Oliver
authors.initials: O
authors.lastname: Quaile
authors.forename: Alexander
authors.initials: A
authors.lastname: Wenk
authors.forename: Christoph
authors.initials: C
authors.lastname: Wigge
authors.forename: Sylvie
authors.initials: S
authors.lastname: Eigeldinger-Berthou
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hirn
authors.forename: Martin
authors.initials: M
authors.lastname: Schäffler
authors.forename: Carsten
authors.initials: C
authors.lastname: Schleh
authors.forename: Winfried
authors.initials: W
authors.lastname: Möller
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
authors.forename: Wolfgang G
authors.initials: WG
authors.lastname: Kreyling
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D004195:Disease Models, Animal; D004337:Drug Carriers; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D005260:Female; D006046:Gold / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000648:ultrastructure; D053768:Metal Nanoparticles; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D053503:Epithelial Sodium Channels; D006046:Gold