Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease

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(1), p. 19. BioMed Central 10.1186/1743-8977-10-19

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Geiser, Marianne; Wigge, Christoph and Eigeldinger, Sylvie

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1743-8977

Publisher:

BioMed Central

Language:

English

Submitter:

Marianne Geiser Kamber

Date Deposited:

02 May 2014 08:42

Last Modified:

18 Jan 2017 10:29

Publisher DOI:

10.1186/1743-8977-10-19

PubMed ID:

23680060

BORIS DOI:

10.7892/boris.47794

URI:

https://boris.unibe.ch/id/eprint/47794

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