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Oral Colon- and Mitochondria-Targeted Nanoparticles Alleviate Ulcerative Colitis by Reeducating Macrophage Polarization via SIRT3/FOXO3a-Mediated Mitochondrial Restoration

Research in animals or cells · Journal of gastroenterology and hepatology · Aug 25, 2026

What this means

BACKGROUND AND Mitochondrial dysfunction in macrophages drives pro-inflammatory M1 polarization in ulcerative colitis (UC). We developed a colon-targeted, mitochondria-directed nanoplatform (KSF@SS31@S100Ns) to restore mitochondrial fitness and alleviate UC.

A plain-English summary is on its way. Until then, this is the start of the authors' own summary.

Tested inAnimals
Who it was tested in
Animals or cells
Kind of research
Research in animals or cells

The science

Original title
Oral Colon- and Mitochondria-Targeted Nanoparticles Alleviate Ulcerative Colitis by Reeducating Macrophage Polarization via SIRT3/FOXO3a-Mediated Mitochondrial Restoration.
Authors
Mei R, Zhang R, Li Z et al.
Journal
Journal of gastroenterology and hepatology
Published
Aug 25, 2026
Study type
Lab or animal study · indexed as animal research

Abstract

Background

Mitochondrial dysfunction in macrophages drives pro-inflammatory M1 polarization in ulcerative colitis (UC). We developed a colon-targeted, mitochondria-directed nanoplatform (KSF@SS31@S100Ns) to restore mitochondrial fitness and alleviate UC.

What they did

Kaempferol-loaded silk fibroin (SF) nanoparticles were conjugated with SS-31 peptide and coated with pH-sensitive Eudragit S100. Physicochemical properties, release profile, and uptake were characterized. Mitochondrial function, macrophage polarization, and SIRT3/FOXO3a signaling were assessed in LPS-stimulated RAW264.7 cells. Efficacy and mechanisms were evaluated in a DSS-induced colitis mouse model.

What they found

Nanoparticles showed uniform size (~307 nm), high stability, and pH-dependent release. SS-31 enhanced macrophage uptake and mitochondrial localization. In vitro, KSF@SS31Ns restored mitochondrial membrane potential and ATP, reduced ROS, promoted mitophagy, and shifted macrophages toward the M2 phenotype via SIRT3/FOXO3a activation. In vivo, oral KSF@SS31@S100Ns accumulated in inflamed colons, reduced disease severity, suppressed pro-inflammatory cytokines, elevated IL-10, restored tight-junction proteins, and increased M2 macrophages. KSF@SS31@S100Ns effectively treats experimental colitis by restoring mitochondrial homeostasis, reprogramming macrophage polarization, and repairing the intestinal barrier, offering a translational nanotherapeutic strategy for UC.

The authors' abstract, grouped under plain headings from its own section labels.

Read it on PubMed ↗

Mei R, Zhang R, Li Z et al. Oral Colon- and Mitochondria-Targeted Nanoparticles Alleviate Ulcerative Colitis by Reeducating Macrophage Polarization via SIRT3/FOXO3a-Mediated Mitochondrial Restoration. Journal of gastroenterology and hepatology. 2026. doi:10.1111/jgh.70668. PMID: 42638278. https://pubmed.ncbi.nlm.nih.gov/42638278/

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