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<p>Severe acute pancreatitis (SAP) is a life-threatening inflammatory disorder with an approximate mortality rate of 40%. Current therapeutic approaches fail to address its complex pathological microenvironment, necessitating novel synergistic strategies. Although mesenchymal stem cells (MSCs) exhibit therapeutic potential, their efficacy is significantly compromised by SAP-associated oxidative stress, hyperinflammation, and gut dysbiosis. Herein, we engineered MSCs with antioxidant nanozyme PDA@MnO<sub>x</sub>, named PDA@MnO<sub>x</sub>-MSCs (<i>Abbr.</i> E-MSCs), to establish a regulatory network for SAP therapy. The PDA@MnO<sub>x</sub> nanozymes not only scavenge reactive oxygen species (ROS) to protect MSCs from oxidative damage but also enable in vivo T<sub>1</sub>-weighted MRI tracking. E-MSCs demonstrated enhanced anti-inflammatory effects, evidenced by reduced levels of TNF-ɑ and IL-6, and restored gut microbiota homeostasis, characterized by increased Bacteroidetes abundance. This further alleviated pancreatic necrosis and systemic inflammation. Notably, the synergistic interaction among PDA@MnO<sub>x</sub> nanozymes, MSCs, and the pathological microenvironment restored ROS-inflammation-microbiota homeostasis, significantly improving SAP outcomes. This study provides a multifunctional strategy integrating therapeutic efficacy, in vivo tracking, and gut microbiota modulation for SAP treatment.</p> Graphical Abstract <p></p>

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PDA@MnOx nanozyme-engineered mesenchymal stem cells for severe acute pancreatitis therapy via modulation of ROS-inflammation-microbiota homeostasis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月30日

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  • Zinan Zhao,
  • Muladili Mutailipu,
  • Tianxiao Mei,
  • Ran Cui,
  • Yongkun Wang,
  • Fuguo Liu,
  • Chunxiu Dong,
  • Wenwen Jia,
  • Zhongmin Liu,
  • Bo Chen,
  • Wenjun Le,
  • Yihui Hu

摘要

Severe acute pancreatitis (SAP) is a life-threatening inflammatory disorder with an approximate mortality rate of 40%. Current therapeutic approaches fail to address its complex pathological microenvironment, necessitating novel synergistic strategies. Although mesenchymal stem cells (MSCs) exhibit therapeutic potential, their efficacy is significantly compromised by SAP-associated oxidative stress, hyperinflammation, and gut dysbiosis. Herein, we engineered MSCs with antioxidant nanozyme PDA@MnOx, named PDA@MnOx-MSCs (Abbr. E-MSCs), to establish a regulatory network for SAP therapy. The PDA@MnOx nanozymes not only scavenge reactive oxygen species (ROS) to protect MSCs from oxidative damage but also enable in vivo T1-weighted MRI tracking. E-MSCs demonstrated enhanced anti-inflammatory effects, evidenced by reduced levels of TNF-ɑ and IL-6, and restored gut microbiota homeostasis, characterized by increased Bacteroidetes abundance. This further alleviated pancreatic necrosis and systemic inflammation. Notably, the synergistic interaction among PDA@MnOx nanozymes, MSCs, and the pathological microenvironment restored ROS-inflammation-microbiota homeostasis, significantly improving SAP outcomes. This study provides a multifunctional strategy integrating therapeutic efficacy, in vivo tracking, and gut microbiota modulation for SAP treatment.

Graphical Abstract