Size effect of fluorescent thiol-organosilica particles on their distribution in the mouse spleen

Abstract

We investigated the distribution of intravenously administered thiol-organosilica particle (thiol-OS) in the spleen to evaluate their size effect in mice. A single administration of particles of thiol-OS containing rhodamine B (Rh) (90, 280, 340, 450, 630, 1110, 1670, and 3030 nm in diameter) was performed. After 24 h, we conducted a combination analysis using histological studies by fluorescent microscopy and quantitative inductively coupled plasma optical emission spectrometry (ICP-OES), which revealed no clear correlation between the particle size and spleen uptake of particle weight and number per tissue weight, and the injection dose. Moreover, Rh with 450 nm diameter (Rh450) showed the highest uptake, and Rh with 340 nm diameter (Rh340) showed the lowest uptake. Histologically, large fluorescent areas in the marginal zone (MZ) and red pulp (RP) of the spleen were observed for all particle sizes, but less in the follicle of white pulp. Using combination analysis using the particle weights of ICP-OES and the fluorescent area, we compared the distributions of each particle in each region. Rh450 had the largest accumulated weight in the MZ and RP. Particles larger than Rh450 showed negative correlations between their sizes and accumulated weight in the MZ and RP. Simultaneous dual administration of particles using Rhs and thiol-OS containing fluorescein (90 nm in diameter) showed the size-dependent difference in cellular distribution and intracellular localization. Immunohistochemical staining against macrophage markers, CD169, and F4/80 showed various colocalization patterns with macrophages that uptook particles, indicating differences in particle uptake in each macrophage may have novel significance.

Keywords: Distribution; Intracellular localization; Macrophages; Size effect; Spleen; Thiol-organosilica particles; Uptake.