2. Academic Validation
  3. 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

  • Adv Sci (Weinh). 2025 Apr 29:e2503903. doi: 10.1002/advs.202503903.
Rong Wang 1 2,  Jianwei Zhu 1 3,  Jinyi Zhou 1,  Jinyang Li 4,  Min Wang 4,  Yuqi Wu 1,  Danshan Zhao 5,  Xiancheng Chen 6,  Xiaoyuan Chen 3,  Yuetong Wang 5,  Jianhua Zou 3
Affiliations

Affiliations

  • 1 Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, 210046, China.
  • 2 Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, Hunan, 410219, China.
  • 3 Departments of Diagnostic Radiology Surgery, Chemical and Biomolecular Engineering and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, 119074, Singapore.
  • 4 Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
  • 5 School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu, 210046, China.
  • 6 Department of Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210029, China.
PMID: 40298904 DOI: 10.1002/advs.202503903
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.

Keywords

M1 reprogramming; PI3K/AKT pathway; ferroptosis; ulcerative colitis.

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