Evidence map›Paper›PMID 24503126›Full record

ArticleGastroenterology2014

Nanoparticles with surface antibody against CD98 and carrying CD98 small interfering RNA reduce colitis in mice.

Bo Xiao, Hamed Laroui, Emilie Viennois, Saravanan Ayyadurai, Moiz A Charania, Yuchen Zhang, Zhan Zhang, Mark T Baker, Benyue Zhang, Andrew T Gewirtz and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.

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23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Bo XiaoCenter for Diagnostics and Therapeutics, Institute for Biomedical Science, Departments of Biology and Chemistry, Georgia State University, Atlanta. Electronic address: bxiao@gsu.edu.
Hamed LarouiCenter for Diagnostics and Therapeutics, Institute for Biomedical Science, Departments of Biology and Chemistry, Georgia State University, Atlanta.
Emilie ViennoisCenter for Diagnostics and Therapeutics, Institute for Biomedical Science, Departments of Biology and Chemistry, Georgia State University, Atlanta; Atlanta Veterans Affairs Medical Center, Decatur.
Saravanan AyyaduraiCenter for Diagnostics and Therapeutics, Institute for Biomedical Science, Departments of Biology and Chemistry, Georgia State University, Atlanta.
Moiz A CharaniaCenter for Diagnostics and Therapeutics, Institute for Biomedical Science, Departments of Biology and Chemistry, Georgia State University, Atlanta.
Yuchen ZhangCenter for Diagnostics and Therapeutics, Institute for Biomedical Science, Departments of Biology and Chemistry, Georgia State University, Atlanta.
Zhan ZhangCenter for Inflammation, Immunity and Infection, Department of Biology, Georgia State University, Atlanta.
Mark T BakerCenter for Diagnostics and Therapeutics, Institute for Biomedical Science, Departments of Biology and Chemistry, Georgia State University, Atlanta.
Benyue ZhangCenter for Inflammation, Immunity and Infection, Department of Biology, Georgia State University, Atlanta.
Andrew T GewirtzCenter for Inflammation, Immunity and Infection, Department of Biology, Georgia State University, Atlanta; Department of Pathology, School of Medicine, Emory University, Atlanta, Georgia.
Didier MerlinCenter for Diagnostics and Therapeutics, Institute for Biomedical Science, Departments of Biology and Chemistry, Georgia State University, Atlanta; Atlanta Veterans Affairs Medical Center, Decatur.
Georgia State University · USEmory University · USVeterans Health Administration · US

Funding

ROLE OF CD98 IN INTESTINAL PERMEABILITYR01DK071594 · NIDDK · GEORGIA STATE UNIVERSITY · PI MERLIN, DIDIER · 2006 to 2017
$3.3M
Neutrophil-Epithelial Interaction Mediated by AdenosineR01DK064711 · NIDDK · GEORGIA STATE UNIVERSITY · PI MERLIN, DIDIER · 2004 to 2013
$3.1M
Role of CD98 Glycoprotein in Intestinal InflammationK01DK097192 · NIDDK · GEORGIA STATE UNIVERSITY · PI LAROUI, HAMED · 2012 to 2016
$500k
NIDDK NIH HHS K01 DK097192NIDDK NIH HHS K01-DK-097192NIDDK NIH HHS R01 DK064711NIDDK NIH HHS R01 DK071594NIDDK NIH HHS R01-DK-071594
6 · The paper itself

Abstract

BACKGROUND &

aimsNanoparticles have been explored as carriers of small interfering RNAs (siRNAs) and might be developed to treat patients with inflammatory bowel disease (IBD). Overexpression of CD98 on the surface of colonic epithelial cells and macrophages promotes the development and progression of IBD. We developed an orally delivered hydrogel that releases nanoparticles with single-chain CD98 antibodies on their surface (scCD98 functionalized) and loaded with CD98 siRNA (siCD98). We tested the ability of the nanoparticles to reduce levels of CD98 in the colons of mice with colitis.

methodsscCD98-functionalized siCD98-loaded nanoparticles were fabricated using a complex coacervation technique. We investigated the cellular uptake and lysosome escape profiles of the nanoparticles in Colon-26 cells and RAW 264.7 macrophages using fluorescence microscopy. Colitis was induced by transfer of CD4(+)CD45RB(high) T cells to Rag(-/-) mice or administration of dextran sodium sulfate to C57BL/6 mice. Mice were then given hydrogel (chitosan and alginate) containing scCD98-functionalized nanoparticles loaded with siCD98 or scrambled siRNA (control) via gavage.

resultsThe scCD98-functionalized nanoparticles were approximately 200 nm in size and had high affinity for CD98-overexpressing cells. The scCD98-functionalized siCD98-loaded nanoparticles significantly reduced levels of CD98 in Colon-26 cells and RAW 264.7 macrophages, along with production of inflammatory cytokines (tumor necrosis factor α, interleukin-6, and interleukin-12). In mice with colitis, administration of the scCD98-functionalized siCD98-loaded nanoparticles reduced colon expression of CD98. Importantly, the severity of colitis was also reduced compared with controls (based on loss of body weight, myeloperoxidase activity, inflammatory cytokine production, and histological analysis). Approximately 24.1% of colonic macrophages (CD11b(+)CD11c(-)F4/80(+)) in the mice had taken up fluorescently labeled siRNA-loaded nanoparticles within 12 hours of administration.

conclusionsNanoparticles containing surface CD98 antibody and loaded with siCD98 reduce expression of this protein by colonic epithelial cells and macrophages, and oral administration decreases the severity of colitis in mice. This nanoparticle in hydrogel (chitosan/alginate) formulation might be developed to treat patients with IBD.

Indexed as

NanoparticlesRNA InterferenceAdministration, OralAlginatesAnimalsCell LineChitosanColitisColonDextran SulfateDisease Models, AnimalFusion Regulatory Protein-1Genetic TherapyGlucuronic AcidHexuronic AcidsHomeodomain ProteinsAlginatesChitosanDextran SulfateFusion Regulatory Protein-1Glucuronic AcidHexuronic AcidsHomeodomain ProteinsHydrogelsInterleukin-12Interleukin-6RAG-1 proteinRNA, Small InterferingSingle-Chain AntibodiesTumor Necrosis Factor-alphaCD98Colitis-Targeted TherapyGene SilencingMouse Model

Identifiers

PMID24503126
PMCPMC3992175
OpenAlexW2144331651

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.