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Three-dimensional quantitative co-mapping of pulmonary morphology and nanoparticle distribution with cellular resolution in non-dissected murine lungs.
ACS Nano 13, 1029-1041 (2019)
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 nondissected ex viva 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 NPs were observed in the 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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
3d Whole Lung Imaging ; 3disco ; Acinar Deposition ; Airway Deposition ; Optical Tissue Clearing ; Pulmonary Nanoparticle Delivery; Of-the-art; Whole-body; Mouse Lungs; Micro-ct; Translocation; Particles; Airway; Morphometry; Aerosols; Design
ISSN (print) / ISBN
1936-0851
e-ISSN
1936-086X
Journal
ACS Nano
Quellenangaben
Volume: 13,
Issue: 2,
Pages: 1029-1041
Publisher
American Chemical Society (ACS)
Publishing Place
1155 16th St, Nw, Washington, Dc 20036 Usa
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Reviewing status
Peer reviewed