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Published on: January 5, 2017
Oral Colon- and Mitochondria-Targeted Nanoparticles Alleviate Ulcerative Colitis by Reeducating Macrophage
Ruya Mei1,2, Rong Zhang2, Zhengyang Li3
1Graduate School, Henan Medical University (formerly known as Xinxiang Medical University), Xinxiang, Henan, People's Republic of China.
Background And Aim:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
