We investigated the distribution of intratracheally administered thiol-organosilica (thiol-OS) particles in mouse lungs. Toward this end, single doses of thiol-OS particles containing fluorescein (140 nm in diameter) (F140) and rhodamine B (Rh) (Rh160, Rh280, Rh420, Rh640, and Rh1630 with diameters of 160, 280, 420, 640, and 1630 nm, respectively) were administered. After 24 h, fluorescence imaging revealed homogeneous fluorescence with a patchier pattern on the lung surface and no difference among the six particle sizes. Simultaneous dual administration of Rh and F140 particles did not reveal any size-dependent differences in the lung surface fluorescence. Fluorescence microscopy of the lung sections revealed a similar tissue distribution in the fluorescent areas of Rhs and F140. Some fluorescent areas showed one type of particle fluorescence or only one fluorescence. Cellular distribution of particles was observed in bronchoalveolar lavage cells and lung sections under a high magnification, and correlative light and electron microscopy revealed large cells with fluorescence corresponding to both particle types and small cells with fluorescence of individual particle types, indicating a cell-subset-dependent particle size effect. Rh280, Rh420, and Rh640 exhibited significant size effects and were taken up by alveolar macrophages. Extracellular particles were observed, indicating that saturation exceeded the particle dose threshold in the alveoli. F140 taken up by small and large macrophages colocalized with CD68, CD11c, and CD11b and correlated with CD11c. The size effect, intracellular localization, and extracellular distribution of particles provide insights into lung and systemic drug delivery.
Keywords: distributions; intracellular localizations; intratracheal injections; macrophages; thiol-organosilica particles.