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Nano Research 2024, 17(3): 1748-1759 https://doi.org/10.1007/s12274-023-5969-3
Research Article | Issue | Published: 31 July 2023

Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease

Show Author's Information 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
Keywords:
antioxidant, synergistic therapy, pyroptosis, inflammatory bowel disease, nanoinhibitors
Topics:
Cell death Targeted drug delivery
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
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Abstract Full text Electronic supplementary material About this article

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.


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Abstract
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Electronic supplementary material
About this article

Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease

Show Author's information 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

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: antioxidant, synergistic therapy, pyroptosis, inflammatory bowel disease, nanoinhibitors

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Publication history
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Acknowledgements

Publication history

Received: 30 March 2023
Revised: 28 June 2023
Accepted: 30 June 2023
Published: 31 July 2023
Issue date: March 2024

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Nos. 82270543, 82170573, 81770556 and 21874066), the National Key R&D Program of China (No. 2019YFA0709200), the Key Research and Development Program of Jiangsu Province (No. BE2021373), the Natural Science Foundation of Jiangsu Province (No. BK20200336), the Fundamental Research Funds for Central Universities, and the Program for Innovative Talents and Entrepreneur in Jiangsu. All animal studies were approved by the Ethics Committee of Jinling Hospital (No. 2021JLHDWLSZ-0010). Surgical specimens were collected from Department of Gastroenterology and Hepatology, General Hospital of Eastern Theater Command. The use of human biopsies was approved by the Ethics Committee of Jinling Hospital (No. 2022DZKY-048-01). All patients enrolled were given informed written consent.

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