Research Article
Imaging of size-dependent uptake and identification of novel pathways in mouse Peyer's patches using fluorescent organosilica particles

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Abstract

We investigated size-dependent uptake of fluorescent thiol-organosilica particles by Peyer's patches (PPs). We performed an oral single-particle administration (95, 130, 200, 340, 695 and 1050 nm) and a simultaneous dual-particle administration using 2 kinds of particles. Histological imaging and quantitative analysis revealed that particles taken up by the PP subepithelial dome were size dependent, and there was an optimal size range for higher uptake. Quantitative analysis of simultaneous dual-particle administration revealed that the percentage of fluorescence areas for 95, 130, 200, 340, 695 and 1050 nm with respect to 110 nm area was 124.0, 89.1, 73.8, 20.2, 9.2 and 0.5%, respectively. Additionally, imaging using fluorescent thiol-organosilica particles could detect 2 novel pathways through mouse PP epithelium: the transcellular pathway and the paracellular pathway. The uptake of nanoparticles based on an optimal size range and 2 novel pathways could indicate a new approach for vaccine delivery and nanomedicine development.

From the Clinical Editor

Studying various sizes of fluorescent organosilica particles and their uptake in Peyer’s patches, this team of authors determined the optimal size range of administration. Two novel pathways through mouse Peyer’s patch epithelium were detected, i.e., the transcellular pathway and the paracellular pathway. This observation may have important applications in future vaccine delivery and nano-drug delivery.

Graphical Abstract

Single-particle and simultaneous dual-particle administration of fluorescent organosilica particles revealed size-dependent uptake and presents novel pathways in mouse Peyer’s patches.

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Section snippets

Materials

Rhodamine B, 3-mercaptopropyltrimethoxysilane (MPMS), (3-Aminopropyl)trimethoxysilane (APS), fluorescein isothiocyanate (FITC) and the lectin Ulex europaeus agglutinin I (UEAI) conjugated to FITC were purchased from Sigma–Aldrich Chemical Co. (Saint Louis, Missouri). Anti-mouse CD11b (Mac 1 α chain) antibody and FITC mouse anti-rat IgG secondary antibody was purchased from eBioscience, Inc., (Kobe, Japan). Paraformaldehyde was purchased from Merck KGaA (Darmstadt, Germany). Osmium tetroxide was

Size and time dependency of fluorescent thiol-organosilica particles uptake by mouse PPs

Figure 2 shows the FM of mouse PPs 1, 3 and 6 hours after oral administration of various sizes of particles containing rhodamine B. The fluorescence from Rh95, Rh130 and Rh200 in the subepithelial dome was increased at 6 hours in comparison with those at 1 and 3 hours. For both Rh340 and Rh695, the fluorescence in the subepithelial dome after 1 and 3 hours was almost similar, but after 6 hours the fluorescence increased. Very little fluorescence was observed in the subepithelial dome for

Discussion

In this study, we orally administered various sizes of fluorescent thiol-organosilica particles to study the size-dependent uptake through PPs. The particles could be taken up by PPs in a way that is similar to that of polystyrene,15, 23, 39 chitosan,4 poly DL-lactide-co-glycolide (PLAGA),40 titanium dioxide particles41 and other particles.19, 22,24, 25, 26, 27, 28, 29 Several physical properties of the NPs can influence their interaction within the M cells and other cells.14, 15, 16, 17, 18 If

Acknowledgments

This work was supported partly by a Grant-in-Aid for Younger Scientists (to M. Nakamura), by a Grant for Practical Application of University Research and Development Results under the Matching Fund Method (to M. Nakamura) from the New Energy and Industrial Technology Development Organization (NEDO) of Japan by a Grant-in-Aid for Scientific Research (C) (to M. Nakamura), and by the financial support of the Egyptian Ministry of Higher Education and Scientific Research, Missions Sector (to A.

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  • Cited by (0)

    We thank the Egyptian Ministry of Higher Education and Scientific Research, Missions Sector for supporting the author (Aziz Awaad).

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