title: Tracking of Inhaled Near-Infrared Fluorescent Nanoparticles in Lungs of SKH-1 Mice with Allergic Airway Inflammation.
abstract: Molecular imaging of inflammatory lung diseases, such as asthma, has been limited to date. The recruitment of innate immune cells to the airways is central to the inflammation process. This study exploits these cells for imaging purposes within the lung, using inhaled polystyrene nanoparticles loaded with the near-infrared fluorescence dye Itrybe (Itrybe-NPs). By means of in vivo and ex vivo fluorescence reflectance imaging of an ovalbumin-based allergic airway inflammation (AAI) model in hairless SKH-1 mice, we show that subsequent to intranasal application of Itrybe-NPs, AAI lungs display fluorescence intensities significantly higher than those in lungs of control mice for at least 24 h. Ex vivo immunofluorescence analysis of lung tissue demonstrates the uptake of Itrybe-NPs predominantly by CD68(+)CD11c(+)ECF-L(+)MHCII(low) cells, identifying them as alveolar M2 macrophages in the peribronchial and alveolar areas. The in vivo results were validated by confocal microscopy, overlapping tile analysis, and flow cytometry, showing an amount of Itrybe-NP-containing macrophages in lungs of AAI mice significantly larger than that in controls. A small percentage of NP-containing cells were identified as dendritic cells. Flow cytometry of tracheobronchial lymph nodes showed that Itrybe-NPs were negligible in lung draining lymph nodes 24 h after inhalation. This imaging approach may advance preclinical monitoring of AAI in vivo over time and aid the investigation of the role that macrophages play during lung inflammation. Furthermore, it allows for tracking of inhaled nanoparticles and can hence be utilized for studies of the fate of potential new nanotherapeutics.
authors.forename: M Andrea
authors.initials: MA
authors.lastname: Markus
authors.forename: Joanna
authors.initials: J
authors.lastname: Napp
authors.affiliation: Biophotonics Division, BAM Federal Institute for Materials Research and Testing , 12205 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Behnke
authors.forename: Miso
authors.initials: M
authors.lastname: Mitkovski
authors.forename: Sebastian
authors.initials: S
authors.lastname: Monecke
authors.forename: Christian
authors.initials: C
authors.lastname: Dullin
authors.affiliation: Aeirtec Limited , Newcastle upon Tyne NE30 1JE, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kilfeather
authors.forename: Ralf
authors.initials: R
authors.lastname: Dressel
authors.affiliation: Biophotonics Division, BAM Federal Institute for Materials Research and Testing , 12205 Berlin, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Resch-Genger
authors.forename: Frauke
authors.initials: F
authors.lastname: Alves
mesh_terms: D000818:Animals; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D008168:Lung / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry*; D011014:Pneumonia / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes
keywords: Itrybe nanoparticles; NIRF; allergic airway inflammation; alveolar macrophages; cell tracking; in vivo near-infrared fluorescence imaging