Multimodal precision imaging of pulmonary nanoparticle delivery in mice: dynamics of application, spatial distribution, and dosimetry

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dc.contributor.authorYang, L.
dc.contributor.authorGradl, R.
dc.contributor.authorDierolf, M.
dc.contributor.authorMöller, W.
dc.contributor.authorKutschke, D.
dc.contributor.authorFeuchtinger, A.
dc.contributor.authorHehn, L.
dc.contributor.authorDonnelley, M.
dc.contributor.authorGünther, B.
dc.contributor.authorAchterhold, K.
dc.contributor.authorWalch, A.
dc.contributor.authorStoeger, T.
dc.contributor.authorRazansky, D.
dc.contributor.authorPfeiffer, F.
dc.contributor.authorMorgan, K.S.
dc.contributor.authorSchmid, O.
dc.date.issued2019
dc.description.abstractTargeted delivery of nanomedicine/nanoparticles (NM/NPs) to the site of disease (e.g., the tumor or lung injury) is of vital importance for improved therapeutic efficacy. Multimodal imaging platforms provide powerful tools for monitoring delivery and tissue distribution of drugs and NM/NPs. This study introduces a preclinical imaging platform combining X‐ray (two modes) and fluorescence imaging (three modes) techniques for time‐resolved in vivo and spatially resolved ex vivo visualization of mouse lungs during pulmonary NP delivery. Liquid mixtures of iodine (contrast agent for X‐ray) and/or (nano)particles (X‐ray absorbing and/or fluorescent) are delivered to different regions of the lung via intratracheal instillation, nasal aspiration, and ventilator‐assisted aerosol inhalation. It is demonstrated that in vivo propagation‐based phase‐contrast X‐ray imaging elucidates the dynamic process of pulmonary NP delivery, while ex vivo fluorescence imaging (e.g., tissue‐cleared light sheet fluorescence microscopy) reveals the quantitative 3D drug/particle distribution throughout the entire lung with cellular resolution. The novel and complementary information from this imaging platform unveils the dynamics and mechanisms of pulmonary NM/NP delivery and deposition for each of the delivery routes, which provides guidance on optimizing pulmonary delivery techniques and novel‐designed NM for targeting and efficacy.
dc.description.statementofresponsibilityLin Yang, Regine Gradl, Martin Dierolf, Winfried Möller, David Kutschke, Annette Feuchtinger, Lorenz Hehn, Martin Donnelley, Benedikt Günther, Klaus Achterhold, Axel Walch, Tobias Stoeger, Daniel Razansky, Franz Pfeiffer, Kaye S. Morgan, Otmar Schmid
dc.identifier.citationSmall, 2019; 15(49):1904112-1-1904112-16
dc.identifier.doi10.1002/smll.201904112
dc.identifier.issn1613-6810
dc.identifier.issn1613-6829
dc.identifier.orcidDonnelley, M. [0000-0002-5320-7756]
dc.identifier.urihttp://hdl.handle.net/2440/122202
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/arc/FT180100374
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1140617
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1160011
dc.rights© 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttps://doi.org/10.1002/smll.201904112
dc.subjectLung
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectMice
dc.subjectMicroscopy, Fluorescence
dc.subjectDrug Delivery Systems
dc.subjectFemale
dc.subjectNanomedicine
dc.subjectNanoparticles
dc.titleMultimodal precision imaging of pulmonary nanoparticle delivery in mice: dynamics of application, spatial distribution, and dosimetry
dc.typeJournal article
pubs.publication-statusPublished

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