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Self-Amplification Immunomodulatory Strategy for Tissue Regeneration in Diabetes Based on Cytokine-ZIFs System

机译:基于细胞因子 - ZIFS系统的糖尿病组织再生的自扩增免疫调节策略

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摘要

Dysfunctional macrophages and excessive inflammatory responses lead to severe tissue regeneration disorders in diabetes. Herein, a function-oriented self-amplification immunomodulatory (SAI) strategy based on an interleukin-33 (IL-33) loaded zeolitic imidazolate frameworks (IL@ZIF) nano-platform is proposed to treat tissue regeneration disorders by restoring macrophage function and reconstructing immune microenvironment in diabetes. It is found that ZIFs effectively protect IL-33 from premature degradation. In the wound area, the released Zn2+ not only improves the antioxidant capacity of macrophages to avoid reactive oxygen species-induced dysfunction, but also upregulates IL-33 receptor (ST2L) expression and triggers M2 macrophages polarization. Subsequently, the released IL-33 significantly amplifies M2 macrophage polarization through IL-33/ST2L signaling, resulting in a reversal of the pro-inflammatory microenvironment of diabetic wounds. This synergistic effect endows the nano-platform with an excellent ability to accelerate tissue regeneration in vitro and in vivo. Overall, this IL@ZIF mediated function-oriented SAI strategy provides new alternatives for the treatment of tissue regeneration disorders in diabetes.
机译:功能障碍巨噬细胞和过度炎症反应导致糖尿病中严重的组织再生障碍。在此,提出了一种基于白细胞介素-33(IL-33)的函数的自扩增免疫调节(SAI)策略,所述沸石咪唑酯骨架(IL ZIF)纳米平台被提出通过恢复巨噬细胞函数和重建来治疗组织再生障碍免疫微环境在糖尿病中。发现Zifs有效地保护IL-33过早降解。在伤口区域,释放的Zn2 +不仅改善了巨噬细胞的抗氧化能力,以避免反应性氧物质诱导的功能障碍,而且还上调IL-33受体(ST2L)表达并触发M2巨噬细胞极化。随后,释放的IL-33通过IL-33 / ST2L信号传导显着放大M2巨噬细胞偏振,导致糖尿病伤口的促炎微环境的逆转。这种协同效果赋予纳米平台,具有优异的能力,以在体外和体内加速组织再生。总的来说,这是IL @ ZIF介导的功能为导向的SAI战略为治疗糖尿病中的组织再生障碍提供了新的替代方案。

著录项

  • 来源
    《Advanced Functional Materials》 |2021年第31期|2100795.1-2100795.13|共13页
  • 作者单位

    Shanghai Jiao Tong Univ Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6 Dept Orthopaed Shanghai 200233 Peoples R China|Fudan Univ Dept Mat Sci Shanghai 200433 Peoples R China;

    Guangzhou Med Univ Sch Pharmaceut Sci Key Lab Mol Target & Clin Pharmacol Guangzhou 511436 Peoples R China|Guangzhou Med Univ Sch Pharmaceut Sci State Key Lab Resp Dis Guangzhou 511436 Peoples R China|Guangzhou Med Univ Affiliated Hosp 5 Guangzhou 511436 Peoples R China;

    Shanghai Jiao Tong Univ Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6 Dept Orthopaed Shanghai 200233 Peoples R China;

    Shanghai Jiao Tong Univ Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6 Dept Orthopaed Shanghai 200233 Peoples R China;

    Shanghai Jiao Tong Univ Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6 Dept Orthopaed Shanghai 200233 Peoples R China;

    Shanghai Jiao Tong Univ Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6 Dept Clin Lab Shanghai 200233 Peoples R China;

    Fudan Univ Dept Mat Sci Shanghai 200433 Peoples R China;

    Shanghai Jiao Tong Univ Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6 Dept Orthopaed Shanghai 200233 Peoples R China;

    Shanghai Jiao Tong Univ Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6 Dept Orthopaed Shanghai 200233 Peoples R China;

    Fudan Univ Dept Mat Sci Shanghai 200433 Peoples R China|Chinese Acad Sci Shanghai Inst Ceram State Key Lab High Performance Ceram & Superfine Shanghai 200050 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    diabetes; interleukin#8208; 33; macrophages; tissue regeneration; zeolitic imidazolate frameworks;

    机译:糖尿病;白细胞介素‐33;巨噬细胞;组织再生;沸石咪唑酯骨架;

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