2. Academic Validation
  3. Alleviating Pyroptosis of Intestinal Epithelial Cells to Restore Mucosal Integrity in Ulcerative Colitis by Targeting Delivery of 4-Octyl-Itaconate

Alleviating Pyroptosis of Intestinal Epithelial Cells to Restore Mucosal Integrity in Ulcerative Colitis by Targeting Delivery of 4-Octyl-Itaconate

  • ACS Nano. 2024 Jul 2;18(26):16658-16673. doi: 10.1021/acsnano.4c01520.
Wenying Li 1,  Dong Chen 2,  Yanmei Zhu 1,  Qiange Ye 3,  Yang Hua 1,  Ping Jiang 4,  Ying Xiang 1,  Yuejie Xu 1,  Yinya Pan 4,  Hua Yang 1,  Yichun Ma 1,  Hang Xu 5 6,  Cheng Zhao 1 4,  Chang Zheng 4,  Changrong Chen 7,  Yun Zhu 1 6,  Guifang Xu 1 4 3 8
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 21008, Jiangsu Province,China.
  • 2 Clinical Stem Cell Center, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
  • 3 Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing 21008, Jiangsu Province,China.
  • 4 Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province,China.
  • 5 School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau SAR 999078, China.
  • 6 Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
  • 7 Department of Emergency Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
  • 8 Department of Gastroenterology, Taikang Xianlin Drum Tower Hospital, Nanjing 21008, Jiangsu Province,China.
PMID: 38907726 DOI: 10.1021/acsnano.4c01520
Abstract

Current therapies primarily targeting inflammation often fail to address the root relationship between intestinal mucosal integrity and the resulting dysregulated cell death and ensuing inflammation in ulcerative colitis (UC). First, UC tissues from human and mice models in this article both emphasize the crucial role of Gasdermin E (GSDME)-mediated Pyroptosis in intestinal epithelial cells (IECs) as it contributes to colitis by releasing proinflammatory cytokines, thereby compromising the intestinal barrier. Then, 4-octyl-itaconate (4-OI), exhibiting potential for anti-inflammatory activity in inhibiting Pyroptosis, was encapsulated by butyrate-modified Liposome (4-OI/BLipo) to target delivery for IECs. In brief, 4-OI/BLipo exhibited preferential accumulation in inflamed colonic epithelium, attributed to over 95% of butyrate being produced and absorbed in the colon. As expected, epithelium barriers were restored significantly by alleviating GSDME-mediated Pyroptosis in colitis. Accordingly, the permeability of IECs was restored, and the resulting inflammation, mucosal epithelium, and balance of gut flora were reprogrammed, which offers a hopeful approach to the effective management of UC.

Keywords

4-octyl-itaconate; Gasdermin E; butyrate; intestinal barrier damage; intestinal epithelial cell; liposome; pyroptosis.

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