Bioinspired Claw‐Engaged Adhesive Microparticles Armed with γGC Alleviate Ulcerative Colitis via Targeted Suppression of Macrophage Ferroptosis

Bioinspired Claw‐Engaged Adhesive Microparticles Armed with γGC Alleviate Ulcerative Colitis via Targeted Suppression of Macrophage Ferroptosis

Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease, characterized by focal iron overload. Herein, we reported that γ‐glutamylcysteine (γGC) deletion in UC lesions intensified the disease by depleting intracellular GSH to induce macrophage ferroptosis, leading to macrophage M1 r...

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Bibliographic Details
Main Authors: Rong Wang, Jianwei Zhu, Jinyi Zhou, Jinyang Li, Min Wang, Yuqi Wu, Danshan Zhao, Xiancheng Chen, Xiaoyuan Chen, Yuetong Wang, Jianhua Zou
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Advanced Science
Subjects:
ferroptosis
M1 reprogramming
PI3K/AKT pathway
ulcerative colitis
Online Access:https://doi.org/10.1002/advs.202503903
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Summary:Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease, characterized by focal iron overload. Herein, we reported that γ‐glutamylcysteine (γGC) deletion in UC lesions intensified the disease by depleting intracellular GSH to induce macrophage ferroptosis, leading to macrophage M1 reprogramming and eventually exacerbating inflammation. To counteract this, the advanced microparticles (MPs)‐based delivery system is selected to encapsulate γGC. The resulting γGC‐MPs displayed the same porous and spiky morphology as their substrate's natural pollens, resulting in improved intestinal adhesion and enhanced lesion contact of γGC‐MPs. Our results demonstrated that exogenous γGC supplementation could inhibit macrophage M1 polarization by restraining ferroptosis, as well as suppressing the PI3K/AKT pathway and TNF signaling pathway. Compared with free γGC, γGC‐MPs significantly alleviated typical UC symptoms in dextran sulfate sodium (DSS)‐induced colitis, evidenced by reduced intestinal inflammation, restored intestinal barrier function, and improved microbiota composition. Consequently, this study addressed critical gaps in understanding the causes of ferroptosis and its impact on macrophage reprogramming in UC, offering a novel synergistic therapeutic strategy for UC.
ISSN:2198-3844

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