Related Experiment Video
Updated: May 3, 2026
Investigating Target Gene Function in a CD40 Agonistic Antibody-induced Colitis Model using CRISPR/Cas9-based Technologies
Published on: June 2, 2021
Nanoparticles with surface antibody against CD98 and carrying CD98 small interfering RNA reduce colitis in mice
Bo Xiao1, Hamed Laroui1, Emilie Viennois2
1Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Departments of Biology and Chemistry, Georgia State University, Atlanta.
Background & Aims:
Nanoparticles 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.
Methods:
scCD98-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.
Results:
The 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.
Conclusions:
Nanoparticles 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.
Insights
Oral nanoparticles loaded with CD98 siRNA and functionalized with CD98 antibodies effectively reduced CD98 expression and colitis severity in mice. This targeted delivery system shows promise for treating inflammatory bowel disease (IBD).
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Gastroenterology
Background:
- Overexpression of CD98 in the colon contributes to inflammatory bowel disease (IBD) development and progression.
- Targeting CD98 offers a potential therapeutic strategy for IBD.
- Nanoparticles serve as effective carriers for therapeutic payloads like small interfering RNAs (siRNAs).
Purpose of the Study:
- To develop and evaluate orally delivered nanoparticles functionalized with CD98 antibodies and loaded with CD98 siRNA (siCD98) for IBD treatment.
- To assess the efficacy of these nanoparticles in reducing CD98 expression in colonic cells and alleviating colitis in a mouse model.
Main Methods:
- Fabrication of scCD98-functionalized, siCD98-loaded nanoparticles via complex coacervation.
- Investigation of nanoparticle cellular uptake and lysosome escape in colon cancer cells and macrophages.
- Induction of colitis in mice using T-cell transfer or dextran sodium sulfate.
- Oral administration of nanoparticles encapsulated in a chitosan/alginate hydrogel to colitis-induced mice.
Main Results:
- Nanoparticles demonstrated high affinity for CD98-overexpressing cells and effectively reduced CD98 levels and inflammatory cytokine production in vitro.
- Oral administration of scCD98-functionalized siCD98 nanoparticles significantly decreased colon CD98 expression in colitis models.
- Treatment led to a notable reduction in colitis severity, evidenced by improved body weight, reduced myeloperoxidase activity, and favorable histological outcomes.
- Approximately 24.1% of colonic macrophages successfully internalized the nanoparticles within 12 hours.
Conclusions:
- Surface-functionalized nanoparticles loaded with siCD98 effectively target and reduce CD98 expression in colonic cells and macrophages.
- Oral administration of this nanoparticle-hydrogel formulation ameliorates colitis severity in mice.
- This innovative therapeutic approach holds potential for clinical development in treating patients with inflammatory bowel disease.
More Related Videos
08:37Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
09:36Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo
Published on: February 5, 2019