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초록

Inflammatory bowel disease (IBD) exhibits pathological heterogeneity driven by multifactorial origins and patient variability, posing therapeutic challenges due to divergent immune microenvironment dynamics. Notably, neutrophils and macrophages showed prominent heterogeneity in IBD patients and underwent different reprogramming during the acute and chronic inflammatory phases. To address this pathological complexity, an orally administered TH@PVP-gel system integrating tanshinone IIA (Tan) and hemin (Hem) was engineered to address the heterogeneity of IBD pathology with the aim of achieving multi-targeted modulation of IBD. TH@PVP-gel specifically promoted neutrophil apoptosis and facilitated macrophage M2 polarization in the inflamed environment of the colon, targeting inflammatory heterogeneity and remodeling the inflammatory environment. In addition, the TH@PVP-gel efficiently scavenged reactive oxygen species (ROS), inhibited the death of colonic epithelial cells, and restored the intestinal barrier. Ultimately, the TH@PVP-gel demonstrated excellent therapeutic efficacy in both acute and chronic colitis, providing a potential strategy for the broad-spectrum treatment of IBD.

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