Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry

Lin 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

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2 Citations (Scopus)

Abstract

Targeted 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.

Original languageEnglish
Article number1904112
Number of pages16
JournalSmall
Volume15
Issue number49
DOIs
Publication statusPublished - 6 Dec 2019

Keywords

  • aerosol inhalation therapy
  • lung fluorescence imaging
  • optical tissue clearing
  • pulmonary delivery
  • X-ray imaging

Cite this

Yang, L., Gradl, R., Dierolf, M., Möller, W., Kutschke, D., Feuchtinger, A., Hehn, L., Donnelley, M., Günther, B., Achterhold, K., Walch, A., Stoeger, T., Razansky, D., Pfeiffer, F., Morgan, K. S., & Schmid, O. (2019). Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry. Small, 15(49), [1904112]. https://doi.org/10.1002/smll.201904112