Histochemical and biochemical analysis of the size-dependent nanoimmunoresponse in mouse Peyer's patches using fluorescent organosilica particles

Abstract

Background/objective The size-dependent mucosal immunoresponse against nanomaterials (nanoimmunoresponse) is an important approach for mucosal vaccination. In the present work, the size-dependent nanoimmunoresponse of mouse Peyer’s patches (PPs) and immunoglobulin A (IgA) level was investigated using fluorescent thiol-organosilica particles. Methods Various sizes of fluorescent thiol-organosilica particles (100, 180, 365, 745, and 925 nm in diameter) were administered orally. PPs were analyzed histochemically, and IgA levels in PP homogenates, intestinal secretions around PPs, and bile were analyzed biochemically. Results When compared with the larger particles (745 and 925 nm), oral administration of smaller thiol-organosilica particles (100, 180, and 365 nm) increased the number of CD11b + macrophages and IgA + cells in the subepithelial domes of the PPs. Additionally, administration of larger particles induced the expression of alpha-L-fucose and mucosal IgA on the surface of M cells in the follicle-associated epithelia of PPs and increased the number of 33D1 + dendritic cells in the subepithelial domes of the PPs. IgA contents in the bile and PP homogenates were high after the administration of the 100 nm particles, but IgA levels in the intestinal secretions were high after the administration of the 925 nm particles. Two size-dependent routes of IgA secretions into the intestinal lumen, the enterohepatic route for smaller particles and the mucosal route for larger particles were proposed. Conclusion Thiol-organosilica particles demonstrated size-dependent nanoimmunoresponse after oral administration. The size of the particles may control the mucosal immunity in PPs and were useful in mucosal vaccination approaches.

Cellular Distribution and Intracellular Localization of Different Sizes of Fluorescent Thiol-Organosilica Particles in Mouse Lungs

“…These immunohistological studies indicate that the colocalization ratios of F140 and each macrophage surface marker were different. Previously, we reported differences in particle uptake of macrophage surface markers as well as particle size in mouse Peyer’s patches using CD11b 10 and in mouse spleens using CD169 and F4/80 . These studies showed that macrophages with the same surface markers also exhibited differences in particle uptake, indicating that macrophages with the same markers can be further classified according to particle uptake.…”

“…Previously, we reported differences in particle uptake of macrophage surface markers as well as particle size in mouse Peyer's patches using CD11b 10 and in mouse spleens using CD169 and F4/80. 11 These studies showed that macrophages with the same surface markers also exhibited differences in particle uptake, indicating that macrophages with the same markers can be further classified according to particle uptake. Classification of macrophages using particle uptake is a new approach.…”

“…We are investigating biological particle size effect on the particle distribution in various organs and tissues. Previously, we reported the size effect of fluorescent thiol-OS particles in the Peyer’s patches, , popliteal lymph nodes, and spleen of mice via various administration routes. These tissues and organs showed differences in the particle distribution depending on the particle size.…”

Preparation of Nanoparticles Including Antisolvent Drugs by the Combination of Roll Milling and High-pressure Homogenization

“…To date, many methods have been developed for micronizing such particles [ 5 , 6 ]. In addition to improving the solubility of the drug due to an increase in the drug particle’s surface area, drugs micronized to the nano-order may also be directly delivered through intestinal Peyer’s patches [ 7 , 8 ].…”

Mesoscopic Multimodal Imaging Provides New Insight to Tumor Tissue Evaluation: An Example of Macrophage Imaging of Hepatic Tumor using Organosilica Nanoparticles

“…Organosilica NPs can contain not only functional molecules such as fluorescent dye 20 , 21 but also nanomaterials 22 , 23 . Functionalized organosilica particles were applied for biomedical research such as imaging in vitro 20 , 22 and in vivo 21 – 25 , and single cell analysis 26 , 27 . In addition functional molecules and nanomaterials could show new function in organosilica nanoparticles 21 – 23 .…”