Three-Dimensional Quantitative Co-Mapping of Pulmonary Morphology and Nanoparticle Distribution with Cellular Resolution in Non-Dissected Murine Lungs.

Yang, Lin; Feuchtinger, Annette; Moeller, Winfried; Ding, Yaobo; Kutschke, David; Möller, Gabriele; Schittny, Johannes; Burgstaller, Gerald; Hofmann, Werner; Stoeger, Tobias; Razansky, Daniel; Walch, Axel; Schmid, Otmar (2019). Three-Dimensional Quantitative Co-Mapping of Pulmonary Morphology and Nanoparticle Distribution with Cellular Resolution in Non-Dissected Murine Lungs. ACS nano, 13(2), pp. 1029-1041. American Chemical Society 10.1021/acsnano.8b07524

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Deciphering biodistribution, biokinetics and biological effects of nanoparticles (NPs) in entire organs with cellular resolution remains largely elusive due to the lack of effective imaging tools. Here, light sheet fluorescence microscopy in combination with optical tissue clearing was validated for concomitant three-dimensional mapping of lung morphology and NP biodistribution with cellular resolution in non-dissected ex vivo murine lungs. Tissue autofluorescence allowed for label-free, quantitative morphometry of the entire bronchial tree, acinar structure and blood vessels. Co-registration of fluorescent NPs with lung morphology revealed significant differences in pulmonary NP distribution depending on the means of application (intratracheal instillation and ventilator-assisted aerosol inhalation under anesthetized conditions). Inhalation exhibited a more homogeneous NP distribution in conducting airways and acini indicated by a central-to-peripheral (C/P) NP deposition ratio of unity (0.98 ± 0.13) as compared to a 2-fold enhanced central deposition (C/P = 1.98 ± 0.37) for instillation. After inhalation most of NPs were observed in proximal part of the acini as predicted by Computational Fluid Dynamics simulations. At cellular resolution patchy NP deposition was visualized in bronchioles and acini, but more pronounced for instillation. Excellent linearity of the fluorescence intensity-dose response curve allowed for accurate NP dosimetry and revealed ca. 5% of the inhaled aerosol was deposited in the lungs. This single-modality imaging technique allows for quantitative co-registration of tissue architecture and NP biodistribution, which could accelerate elucidation of NP biokinetics and bioactivity within intact tissues facilitating both nanotoxicology studies and the development of nanomedicines.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Schittny, Johannes

Subjects:

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

ISSN:

1936-0851

Publisher:

American Chemical Society

Language:

English

Submitter:

Johannes Schittny

Date Deposited:

28 Feb 2019 14:16

Last Modified:

05 Nov 2019 13:20

Publisher DOI:

10.1021/acsnano.8b07524

PubMed ID:

30566327

BORIS DOI:

10.7892/boris.124101

URI:

https://boris.unibe.ch/id/eprint/124101

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