首页|Thiol—Disulfide Exchange Coordinates the Release of Nitric Oxide and Dexamethasone for Synergistic Regulation of Intestinal Microenvironment in Colitis

Thiol—Disulfide Exchange Coordinates the Release of Nitric Oxide and Dexamethasone for Synergistic Regulation of Intestinal Microenvironment in Colitis

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The cell-specific functions of nitric oxide(NO)in the intestinal microenvironment orchestrate its therapeutic effects in ulcerative colitis.While most biomaterials show promise by eliciting the characteristics of NO,the insufficient storage,burst release,and pro-inflammatory side effects of NO remain as challenges.Herein,we report the development of thiol-disulfide hybrid mesoporous organosilica nanoparticles(MONs)that improve the storage and sustained release of NO,broadening the therapeutic window of NO-based therapy against colitis.The tailored NO-storing nanomaterials coordinated the release of NO and the immunoregulator dexamethasone(Dex)in the intestinal microenvironment,specifically integrating the alleviation of oxidative stress in enterocytes and the reversal of NO-exacerbated macrophage activation.Mechanistically,such a synchronous operation was achieved by a self-motivated process wherein the thiyl radicals produced by NO release cleaved the disulfide bonds to degrade the matrix and release Dex via thiol-disulfide exchange.Specifically,the MON-mediated combination of NO and Dex greatly ameliorated intractable colitis compared with 5-aminosalicylic acid,even after delayed treatment.Together,our results reveal a key contribution of synergistic modulation of the intestinal microenvironment in NO-based colitis therapy and introduce thiol-disulfide hybrid nanotherapeutics for the management of inflammatory diseases and cancer.

Junna Lu、Tongfei Shi、Chengxin Shi、Fangman Chen、Chao Yang、Xiaochun Xie、Zheng Wang、He Shen、Jiaqi Xu、Kam W.Leong、Dan Shao

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School of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou International Campus,Guangzhou,Guangdong 510006,China

National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangdong 510006,China

Department of Plastic and Aesthetic Center,The First Affiliated Hospital of Zhejiang University,Hangzhou 310000,China

Department of Biomedical Engineering,Columbia University,New York,NY 10027,USA

School of Medicine,South China University of Technology,Guangzhou,Guangdong 510006,China

CAS Key Laboratory of Nano-Bio Interface,Suzhou Institute of Nano-Tech and NanoBionics,Chinese Academy of Sciences,Suzhou 215123,China

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety,CAS Center for Excellence in Nanoscience,National Center for Nanoscience and Technology,Beijing 100190,China

Guangdong Provincial Key Laboratory of Biomedical Engineering,South China University of Technology,Guangzhou 510006,China

Key Laboratory

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFundamental Research Funds for the Central Universities

8207204932271388

2024

10.34133/research.0204

研究(英文)

研究(英文)

CSTPCD
ISSN：
年,卷(期)：2024.2024(2)
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