Localization of alpha 2,6-linked sialic acid residues in gastrointestinal tract compartments of some tetrapod's representatives: Comparative histochemical study.

Epithelial mucins composed mainly of glycoproteins and play a vital role as protective barrier against a variety of harmful molecules and microbial infection. Additionally sialic acids, like glycoproteins, are considered as a main component of epithelial mucins and play an important role in mucosal immunity. For example, alpha 2,6-linked galactose/N-acetyl-galactosamine (Gal/GalNAc) sialic acid residues can recognize and mask different biological sites in some intermolecular or intercellular interactions. In this study, the localization sites relationship between general mucins and alpha 2,6-linked Gal/GalNAc sialic acid residues in different compartments in gastrointestinal tract (GIT) of tetrapod representatives were investigated using lectin histochemistry. The toad (Bufo regularis), lizard (Trachylepis quinquetaeniata), pigeon (Columba livia domestica) and mouse (Mus musculus) were used as amphibian, reptilian, avian and mammalian representatives respectively. In general, the biodistribution sites of mucins are localized in most compartment sites and partially overlapped with the sites of sialic acid residues in some compartment in each animal representative. Additionally, the localization sites of both mucins and sialic acid in the GIT regions differ based on the tissue type in each tetrapod representative. The mucosa of oesophagus in the toad and lizard showed higher positive signal of general mucins compared with other tetrapod representatives. However, the mucosa of the oesophagus in the toad revealed a positive signal of sialic acid in the tubular glands only, whereas the lizard's mucosa showed a positive signal of sialic acid in the goblet cells. Additionally, the pigeon's oesophagus showed no localization of the sialic acid or mucins while, all layers of the mouse's oesophagus showed a positive localization of the sialic acid residues. In the stomach, all stomach mucosa compartments in all representatives showed positive signal of mucins, while the gastric glands in the toad, pigeon (proventricular glands) and mouse showed signals of sialic acid residues localization but in different trends. While the lizard showed a localization of the sialic acid in the mucosal lamina propria only. Furthermore, the mucosa of the ileum showed positive signal of mucin in the goblet cells and some absorptive cells brush borders in all tetrapod animals. While a higher signal of the sialic acid residues in the absorptive cells but not the goblet cells in the case of the toad and mouse. While the lizard's ileum showed a higher localization of sialic acid in the goblet cells only. Mucin localization in the rectum was similar to those in ileum. Specifically, the toad and lizard showed signals of the sialic acid residues in the goblet cells only, while the mouse's rectum showed a higher signal of sialic acids in the absorptive cells and lamina propria but not in the goblet cells. The present study introduces important data about the biodistribution and localization profiles of general mucins and sialic acids residues in the GIT different compartments in each representative of tetrapoda animals. Further studies are needed to investigate the important role of sialic acid residues localization in different compartments of GIT mucosa.

Time-dependent biodistribution profiles and reaction of polyethylene glycol-coated iron oxide nanoclusters in the spleen after intravenous injection in the mice.

Polyethylene glycol (PEG) is widely used polymer in the field of pharmaceutics, particularly in which related to drug delivery systems (DDS). Surface coating of the nanoparticles (NPs) with PEG (i.e. pegylation) adds novel characteristics that make their use in vivo more effective with lower cytotoxicity. The biodistribution profiles, reaction, and fate of PEG-coated NPs in vivo still unclear and need more detailed studies. Here in this study, we prepared PEG-coated iron oxide nanoclusters (PEG-coated IONCs) to investigate their biodistribution profiles and reactions in spleen after intravenous injection time-dependently. Using Prussian blue staining method as specific histochemical reaction for iron detection in the tissues, the PEG-coated IONCs were observed in a higher ratio in spleen red pulp after 1 day of injection but decreased time-dependently after 10 days and 20 days. Interestingly, PEG-coated IONCs moved from red pulp into the white pulp specially after 20 days of injection. After long time exposure (20 days), higher amount of PEG-coated IONCs was observed in the center of spleen white pulp follicle. Using histological staining, the reaction of PEG-coated IONCs with splenocytes or immune cells induced cellular abnormalities such as, nucleic acid damages, induction of megakaryocytes number, and sever vacuolation in the white pulp area specially after 20 days of injection. Histochemically, the localization of PEG-coated IONCs in the splenic parenchyma induced the level of the collagen fibers particularly after 1 day and 10 days of injection. Interestingly, cellular abnormalities in the splenic red pulp as well as collagen levels decreased after 20 days of injection due to the clearance of PEG-coated IONCs from this area. This data indicated that cytotoxicity produced by the reaction of PEG-coated IONCs in the spleen are reversible specially after 20 days of in the intravenous injection. Understanding the detailed mechanism of the fate and reaction of the coated nanomaterials after intravenous injection is important to design effective and safe DDS based NPs.

Changeable net charge on nanoparticles facilitates intratumor accumulation and penetration.

The Enhanced Permeability and Retention (EPR) effect is a golden strategy for the nanoparticle (NP)-based targeting of solid tumors, and the surface property of NPs might be a determinant on their targeting efficiency. Poly(ethylene glycol) (PEG) is commonly used as a shell material; however, it has been pointed out that PEG-coated NPs may exhibit accumulation near tumor vasculature rather than having homogenous intratumor distribution. The PEG shell plays a pivotal role on prolonged blood circulation of NPs but potentially impairs the intratumor retention of NPs. In this study, we report on a shell material to enhance tumor-targeted delivery of NPs by maximizing the EPR effect: polyzwitterion based on ethylenediamine-based carboxybetaine [PGlu(DET-Car)], which shows the changeable net charge responding to surrounding pH. The net charge of PGlu(DET-Car), is neutral at physiological pH 7.4, allowing it to exhibit a stealth property during the blood circulation; however, it becomes cationic for tissue-interactive performance under tumorous acidic conditions owing to the stepwise protonation behavior of ethylenediamine. Indeed, the PGlu(DET-Car)-coated NPs (i.e., gold NPs in the present study) exhibited prolonged blood circulation and remarkably enhanced tumor accumulation and retention than PEG-coated NPs, achieving 32.1% of injected dose/g of tissue, which was 4.2 times larger relative to PEG-coated NPs. Interestingly, a considerable portion of PGlu(DET-Car)-coated NPs clearly penetrated into deeper tumor sites and realized the effective accumulation in hypoxic regions, probably because the cationic net charge of PGlu(DET-Car) is augmented in more acidic hypoxic regions. This study suggests that the changeable net charge on the NP surface in response to tumorous acidic conditions is a promising strategy for tumor-targeted delivery based on the EPR effect.

Comparative microanatomical and histochemical biodistribution profiles of different types of mucins in the intestinal mucosa of some tetrapod representatives.

The microanatomical features of the intestinal tract mucosa layer in different species of tetrapoda vary according to the type of species, tissue, and function of the targeted cells. In the present study, we have evaluated the histological and histochemical variations of the intestinal tract in four species representing superclass tetrapoda. Bufo regularis (toad), Trachylepis quinquetaeniata (lizard), Columba livia domestica (pigeon) and Mus musculus (mouse) were used as representatives for amphibians, reptilians, avians and mammalians respectively. Histologically, the ileum's mucosal layer of the lower tetrapods (toad and lizard) was almost similar and consists of elongated finger-like shape villi lined with simple columnar epithelium and goblet cells. Similarly, the microanatomical features in ileum of higher tetrapod representatives (pigeon and mouse) were characterized by the presence of villi lined with simple columnar epithelium and scattered goblet cells as well as intestinal glands (crypts of Lieberkühn) at the bases of the intestinal villi. In the toad rectum, the mucosal layer was similar to that of the ileum but with shorter villi and more numerous goblet cells. However, the mucosal layer of the rectum in the lizard had low numbers of absorptive columnar epithelial cells with abundant goblet basal cells. Comparatively, the pigeon's rectal mucosa had almost a similar structure to that of ileum but in leaf-like shaped villi. Finally, the rectum of the mouse has narrow rectal pits, instead of villi, lined with goblet cells and absorptive epithelial cells. Histochemically, the ileum in the four studied tetrapod representatives showed varying biodistribution profiles of neutral, sulfated and carboxylated mucins. There are variations encountered in the intestinal brush border and goblet cells of villi in all species as well as the crypts of Lieberkühn in higher tetrapods. Also, the rectum of all tetrapod species showed weak to strong positive signals for the three types of mucins in the brush border and goblet cells of villi in all species and crypts of Lieberkühn in higher tetrapods as well. In addition, the brush border of toad's rectum was lacking sulfated mucins and that of the lizard did not have any type of mucins. The data of this study will contribute to understand the relationship between the microanatomical features and mucins biodistribution profiles in the mucosal layer of tetrapod intestinal tract and their functions.

A higher dose of PEGylated gold nanoparticles reduces the accelerated blood clearance phenomenon effect and induces spleen B lymphocytes in albino mice.

Polyethylene glycol (PEG) is a multifunctional polymer that has many uses in medical and biological applications. Recently, PEG has been mainly used in developing nanomaterial-based drug delivery systems (DDS). PEG is characterized by its high solubility, biological inertness, and ability to escape from immune cells (stealthiness) after systemic injection. The most challenging problem for PEGylated nanomaterials is their rapid elimination from the bloodstream after repeated doses of systemic injection, called accelerated blood clearance (ABC). Therefore, in this study, the effect of PEGylated nanomaterial dose concentration on ABC induction will be investigated using quantitative, histological, and immunohistochemical analyses. A higher dose concentration (2 mg/kg) of PEGylated gold nanoparticles (PEG-coated AuNPs) reduced the ABC phenomenon when intravenously injected into mice preinjected with the same dose. In contrast, a lower dose concentration (< 1 mg/kg) significantly induced the ABC phenomenon by the rapid elimination of the second dose of PEG-coated AuNPs from the bloodstream. To explain the relationship between the dose concentration (from PEG and AuNPs) and the induction of ABC, the biodistribution of PEG-coated AuNPs in liver and spleen [reticuloendothelial systems (RES)-rich organs] was investigated. The injected dose of PEG-coated AuNPs accumulated mainly in the hepatic Kupffer cells and hepatocytes. Similarly, spleen red pulp received a higher amount of the injected dose of PEG-coated AuNPs. However, the biodistriution profiles of PEG-coated AuNPs after the first and second dose for different dose concentrations varied in RES-rich organs. Additionally, the number of B lymphocytes, which have an important role in producing anti-PEG immunoglobulin (Ig)M, was affected by the repeated dose of PEG-coated AuNPs in the spleen. Therefore, for effective nanomaterial-based DDS development, dose optimization of PEG molecules that express PEGylated nanomaterials is important to reduce the ABC phenomenon effect. The ideal concentration of PEG molecules used to coat nanomaterials and the role of RES-rich organs must be determined to control the ABC phenomenon effect of PEGylated nanomaterials.

Comparative microanatomical and histochemical biodistribution profiles of different types of mucins in oesophageal gastric tract mucosa of some tetrapod representatives.

The microanatomical features of the oesophageal gastric tract in tetrapod representatives and their function, especially those related to the mucosal layer, have not yet been fully investigated. The mucosal layer cells and their function in the oesophageal gastric tract differ structurally and functionally in tetrapod representatives based on interspecies difference and the type of food and feeding habits. The present study was, therefore, postulated to compare the mucosal microanatomical structure and histochemical biodistribution of different mucin types in oesophageal gastric tract tissues of four tetrapod species. A representative of each tetrapod class was selected, as follows: the Egyptian toad Bufo regularis, the lizard Trachylepis quinquetaeniata, the domestic pigeon Columba livia domestica and the albino mouse Mus musculus for Amphibia, Reptilia, Aves and Mammalia, respectively. Microanatomically, in lower tetrapods (toad and lizard), the mucosal layer of the oesophagus was composed of simple ciliated columnar epithelium with goblet cells, whereas in higher tetrapods (pigeon and mouse) it was composed of stratified squamous epithelium, with non-keratinised epithelium in the pigeon but keratinised epithelium in the mouse. However, the gastric mucosal layer of the stomach in lower tetrapods consists of simple columnar epithelium and gastric glands. Similarly, the mucosa of the pigeon's proventriculus consists of simple columnar epithelium with proventricular glands opened into the lumen, whereas mouse mucosa consists of simple columnar epithelium which folds and forms gastric glands with gastric pits having a variety of cell types. Histochemically, the neutral mucin profile biodistribution in the oesophagus mucosal layer was variable. It was strongly positive in the toad and lizard, but was weak in the pigeon and completely negative in the mouse. In contrast it was strongly positive in the gastric mucosa of the toad, lizard and pigeon, but was weak in the mouse's gastric mucosa. On the other hand, the signals of carboxylated and sulfated mucins were found to be different. They were strong in the mucosa of the lizard oesophagus. In contrast, the carboxylated mucins in the gastric mucosa were positive in all representatives except the mouse. The sulfated mucins were, however, seen localised in the mucosal layer cells of the lizard and pigeon only. The study revealed that the microanatomical structures and functions as well as mucin distribution profiles in the oesophageal gastric tract are in line with interspecies difference and the type of food and feeding habits. However, this may need further investigations including more tetrapod representatives.

Iron biodistribution profile changes in the rat spleen after administration of high-fat diet or iron supplementation and the role of curcumin.

Curcumin as active metal chelating and antioxidant agent has a potential role in metal reduction and free radicals' neutralization in tissues. Of note, long-term administration of high fat diet (HFD) is considered as a main factor of blood serum iron deficiency. This study aimed to investigate the biodistribution profiles of iron in the spleen after long-term administration of HFD along with iron supplementation. Furthermore, the ameliorative role of curcumin to reduce iron accumulation level and improve the histological abnormalities produced by iron in spleen will be evaluated in the rats. Treated albino rats of this experiment were divided into six groups. Group I was a control group where group II was treated with HFD. Group III and group IV were treated with combination of HFD and curcumin or HFD and iron supplement respectively. Additionally, group V and group VI were treated with combination of HFD, iron supplement and curcumin or curcumin only respectively. Mainly histological analysis was used to investigate iron biodistribution and induced abnormalities in spleen under light microscope. The histochemical specific staining of iron in the spleen showed different biodistribution profiles of iron in the spleen. Administration of the HFD or HFD and iron supplementation increased the iron accumulation in the spleen. Where, curcumin administration with HFD (Group III) or with HFD and iron supplementation (Group V) significantly reduced the iron levels in the spleen. The splenic tissue inflammation, cellular apoptosis and fibrosis produced by higher iron accumulation was ameliorated after administration of curcumin supplementation as shown in the animals treated with HFD/curcumin (Group III) or HFD/iron supplement/curcumin (Group V). This study recommended that, it is preferable to use iron supplementation along with curcumin supplement for less than 4 months to avoid additional iron accumulation in the healthy organs.

Size-dependent biodistribution of thiol-organosilica nanoparticles and F4/80 protein expression in the genital tract of female mice after intravaginal administration.

Recently the vaginal route consider as an ideal route for drug delivery systems (DDS) administration. This is because, it is suitable for lower drug dosage, higher drug concentration in the genital tract tissues and lower drug concentration in pregnant women blood circulation. However, the vaginal route administration faces many challenges due to the physiology as well as the complexity of vaginal tissue histology. Here in this study, during diestrus stage (optimal condition for foreign substance internalization), single or dual size of fluorescent thiol-organosilica nanoparticles (tOS-NPs) were administrated intravaginally. The biodistribution and reactivity of tOS-NPs in different tissues of the female genital tract were investigated under the fluorescence microscope. Furthermore, using immunohistochemical staining, the expression of F4/80 protein and the role of macrophages in transport and re-location of tOS-NPs from vaginal lumen into different genital tissues or other organs were investigated. This study showed that, tOS-NPs size and type of tissue are important in biodistribution and uptake of tOS-NPs in the genital tract. Small size (100 nm) of tOS-NPs was highly accumulated in the genital tract tissues especially endometrial epithelium compared with large tOS-NPs (1000 nm). Contradictory, the large size induced the expression of F4/80 protein and the number of vaginal macrophages compared with small size. However, both small and large sizes of tOS-NPs were found co-localized with F4/80+ macrophages, located in the vaginal, endometrial and ovarian tissues. The tOS-NPs intravaginally administrated were found in the splenic tissues, indicating its ability to enter the blood circulation from the vaginal lumen. Additionally, the high accumulation of tOS-NPs in the endometrial epithelium indicated the endometrial first pass effect of tOS-NPs. As a result, high concentration of tOS-NPs in the endometrial epithelium may reduce the concentration of tOS-NPs-based DDS in the blood circulation and their side effects. Furthermore, during vaginal tissue optimal condition (diestrus stage), understanding the fate and biodistribution of tOS-NPs will introduce important data about the development of save and effective DDS for the pregnant women.

The biodistribution of melanomacrophages and reactivity of PEG or amine-functionalized iron oxide nanoclusters in the liver and spleen of Egyptian toad after intraperitoneal or oral injections: Histochemical study.

Recently, toad flesh is the main source of protein for many peoples. Of note, disease treatment of amphibian animals is a big challenge facing toad farms development. Iron oxide nanoclusters (IONCs) are approved by the Food and Drug Administration (FDA) as new materials for drug delivery systems development. The biodistribution and fate of IONCs in the lower vertebrate tissues such as toads is novel and should be studied in details. In this study, the biodistribution and toxicities of polyethylene glycol-functionalized IONCs (PEG-IONCs) and amine-functionalized IONCs (NH2-IONCs) in the liver and spleen of Egyptian toad were studied after intraperitoneal or oral injections. The localization and levels of IONCs in liver and spleen depends on the root of injection and the surface functionalization. The presence of IONCs in the liver and spleen produced sever to mild histological and histochemical abnormalities, but in a different ratio. The change of melanomacrophages (MMs) numbers depends on the root of injection or the function group on the surface of IONCs and this explains the abnormalities of MMs produced by IONCs treatment. Further, the function group on the surface may control the biodistribution of MMs and abnormalities produced by IONCs in the liver and spleen. Understanding the biodistribution and histological abnormalities of IONCs in the lower vertebrate tissues (amphibians in this study) might introduce important information to develop new drugs which can be used for amphibian diseases treatment or diagnosis. Further, the histopathological and MMs abnormalities produced by IONCs may consider as biomarkers for amphibians diseases diagnosis.

An Ethylenediamine-based Switch to Render the Polyzwitterion Cationic at Tumorous pH for Effective Tumor Accumulation of Coated Nanomaterials.

Polyzwitterions are employed as coating polymers for biomaterials to induce an antifouling property on the surface. Fine-tuning the betaine structure switches the antifouling property to be interactive with anionic tissue constituents in response to a tumorous pH gradient. The ethylenediamine moiety in the carboxybetaine enabled stepwise protonation and initiated the di-protonation process around tumorous pH (6.5). The net charge of the developed polyzwitterion (PGlu(DET-Car)) was thus neutral at pH 7.4 for antifouling, but was cationic at pH 6.5 for interaction with anionic constituents. Quantum dots coated with PGlu(DET-Car) exhibited comparable stealth and enhanced tumor accumulation relative to the PEG system. The present study provides a novel design of smart switchable polyzwitterion based on a precise control of the net charge.

Immunotoxicity of skin acid secretion produced by the sea slug Berthellina citrina in mice spleen: Histological and Immunohistochemical study.

Acid secretion containing sulfuric and hydrochloric acids is a fascinating defensive phenomenon within many groups of marine organisms. This study aimed to investigate the mice spleen histology and immunotoxicity using skin acid secretion (SAS) of the sea slug Berthellina citrina after oral administration. The spleen showed atrophy in the white pulp, decrease in the splenocytes density, megakaryocytes cytoplasmic degeneration as well as inflammatory cells infiltrations. The white and red pulp splenocytes number decreased time-dependently in the treated spleens. Additionally, the size of the megakaryocytes increased as compared with the control. The administration with SAS increased the number of the IgA(+) cells aggregation in the splenic red pulp. Furthermore, after 7days of the administration, large number of dispersed IgA(+) cells were distributed in splenic parenchyma. The IgA(+) cells numbers increased time-dependently as compared with those in the control. The aggregation sizes and number of the F4/80(+) cell in the splenic red pulp were increased. Furthermore the F4/80(+) cells numbers increased time-dependently as compared with those in the control. The UEAI(+) cells were found as free cells but not in aggregations in the control splenic red pulp. Contradictory to the number of IgA(+) cells and F4/80(+) cells the number of the UEAI(+) cells decreased time-dependently after administration with SAS. Hematologically, abnormal numbers of WBCs different cells were observed after administration with SAS. This study provides new insight about the toxicity of a marine extract may be used in natural products industry or medical applications.

Lectin histochemistry shows the comparative biosynthesis and cellular biodistribution of alpha L-fucose residues in some tissues of tetrapoda representatives.

Fucose is a monosaccharide that plays several immunological roles. This study investigated the comparative biosynthesis and cellular biodistribution of fucose residues in some tissues of tetrapoda representatives using lectin histochemistry. In this study, the mouse was used as a representative for mammalian, pigeon for avian, lizard for reptilian, and toad for amphibians. The localization of the fucose residues was seen in several cell types of mice ileum, such as villi microfold (M) cells, goblet cells, some of intestinal crypts cells, and lamina propria cells. In other tetrapoda representatives, fucose was only seen in M cells of lizard ileum and some cells of villi lamina propria of pigeon, lizard, and toad. It was also observed in the pancreatic acinar cells of the mouse and some cell aggregations of pancreatic parenchyma of the lizard. Contrarily, it was not seen either in pigeon or in toad pancreases parenchyma. Spleen of all animals showed the fucose residues in some splenic cells in the red pulp only, barring the white pulp. The liver parenchyma of all tetrapoda representatives hadn't fucose residues. The fucose cellular biodistribution in some cells of tetrapoda representatives differed based on the cell type. In the mouse, it was highly seen in the apical cytoplasm of the villi M cells as well as in the cup-like part of goblet cells. In addition, it was seen as "rings" in the granule membranes of the Ulex europeaus agglutinin I (UEAI(+)) cells in the intestinal crypts cells. Furthermore, the UEAI(+) cells in the lamina propria showed fucose granules in their cytoplasm. There is no clear evidence about the relation between the cellular biosynthesis of fucose residues and mucosal immune cells. The role of fucose residues in the pancreatic acinar cells are not well understood and need further investigations. In this study, fucose residues were synthesized in several types of cells in the mouse ileum, spleen and pancreas as compared with other tetrapoda. The data obtained from this study can help us to get more information about the cellular biodistribution and synthesis of fucose residues in several animal species rather than mammalians.

Time-lapse fluorescence imaging and quantitative single cell and endosomal analysis of peritoneal macrophages using fluorescent organosilica nanoparticles.

Fluorescent thiol-organosilica nanoparticles with 100 nm diameter (F-thiol-OS-100) were applied for time-lapse fluorescence imaging. The evaluation of F-thiol-OS-100 for quantitative analysis demonstrated great advantages as compared with quantum dots and organic fluorescent dye. Time-lapse fluorescence imaging of mouse peritoneal macrophages using F-thiol-OS-100 clearly demonstrated cellular uptake, and single cell analysis showed various patterns of uptake kinetics that could be quantitatively evaluated. We also performed quantitative analysis of endosomal uptake and movements in single cells. A correlation between morphologic findings and endosomal uptake and movement over time was also observed and analyzed quantitatively. The F-thiol-OS-100 showed high potential as a new fluorescence marker for time-lapse fluorescence imaging and quantitative single cell functional analysis for nanomedicine development. FROM THE CLINICAL EDITOR: In this study the authors report on 100 nm thiol-organosilica nanoparticles as time-lapse flurescent markers. F-thiol-OS-100 proved to be superior to quantum dots and organic flurescent dyes, and enabled quantitative single cell functional analysis.

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

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.

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

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.