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Research Article

Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease

Zhenxing Zhu1, Dongtao Zhou2, Yi Yin3, Zhun Li1, Zhen Guo1, Yongchun Pan2, Yanfeng Gao2, Jingjing Yang4, Weiming Zhu1( ), Yujun Song2( ), Yi Li1( )
Department of General Surgery, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing 210093, China
College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210023, China
Department of General Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210008, China
Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
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Graphical Abstract

As an orally administrated therapy strategy, DXMS@CuM@PPADT@PSS (DCMP) responds to reactive oxygen species (ROS) to release drugs and active sites in the lesions of inflammatory bowel disease. DCMP can inhibit NLRP3/GSDMD (nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3/gasdermin D) pathway-related pyroptosis of intestinal epithelial cells and then alleviate the colitis.

Abstract

Inflammatory bowel disease (IBD) is an autoimmune gastrointestinal disease characterized by chronic relapsing inflammation of the intestine. Excessive pyroptosis that exists in the inflamed intestine can activate damage signals and aggravate local inflammation in IBD. Here, we designed an oral pyroptosis nanoinhibitor, DXMS@CuM@PPADT@PSS (DCMP), which can target intestinal lesions, and respond to reactive oxygen species (ROS) to release active sites and drugs at the lesion. DCMP can inhibit the activation of the nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3 (NLRP3) inflammasomes by scavenging ROS, resulting in the down-regulation of gasdermin D (GSDMD) cleavage thus inhibiting pyroptosis. It also improved intestinal barrier function, decreased inflammatory cytokine levels, and increased the diversity of gut microbiota in mice with colitis. This work is believed to expand the biomedical application of nanomaterials for innate immunity modulation.

Keywords

inflammatory bowel diseasenanoinhibitorspyroptosissynergistic therapyantioxidant

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Nano Research
Volume 17 Issue 3,
March 2024
Pages 1748-1759
DOI: 10.1007/s12274-023-5969-3
Cite this article:
Zhu Z, Zhou D, Yin Y, et al. Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease. Nano Research, 2024, 17(3): 1748-1759. https://doi.org/10.1007/s12274-023-5969-3
Topics:
Cell death Targeted drug delivery

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Received: 30 March 2023
Revised: 28 June 2023
Accepted: 30 June 2023
Published: 31 July 2023
© Tsinghua University Press 2023
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