eprintid: 19730
rev_number: 12
eprint_status: archive
userid: 1589
dir: disk0/00/01/97/30
datestamp: 2016-02-03 09:51:44
lastmod: 2024-04-09 20:40:58
status_changed: 2016-02-03 09:51:44
type: article
metadata_visibility: show
creators_name: Geiser, Marianne
creators_name: Quaile, Oliver
creators_name: Wenk, Alexander
creators_name: Wigge, Christoph
creators_name: Eigeldinger-Berthou, Sylvie
creators_name: Hirn, Stephanie
creators_name: Schäffler, Martin
creators_name: Schleh, Carsten
creators_name: Möller, Winfried
creators_name: Mall, Marcus A.
creators_name: Kreyling, Wolfgang G.
title: Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease
subjects: ddc-610
divisions: i-910500
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. Diseased lungs are of specific interest, since these are the main recipients of inhalation therapy. We, therefore, used Scnn1b-transgenic (Tg) mice as a model of chronic obstructive pulmonary disease (COPD) and compared uptake and localization of inhaled AuNP in surface macrophages and lung tissue to wild-type (Wt) mice.   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.  
date: 2013
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 1653740299
own_urn: urn:nbn:de:bsz:16-heidok-197308
language: eng
bibsort: GEISERMARICELLULARUP2013
full_text_status: public
publication: Particle and fibre toxicology
volume: 10
number: 19
place_of_pub: London
pagerange: 1-10
issn: 1743-8977
citation:   Geiser, Marianne ; Quaile, Oliver ; Wenk, Alexander ; Wigge, Christoph ; Eigeldinger-Berthou, Sylvie ; Hirn, Stephanie ; Schäffler, Martin ; Schleh, Carsten ; Möller, Winfried ; Mall, Marcus A. ; Kreyling, Wolfgang G.  (2013) Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease.  Particle and fibre toxicology, 10 (19).  pp. 1-10.  ISSN 1743-8977     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19730/1/12989_2013_Article_244.pdf