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Background <p>Systemic lupus erythematosus (SLE) is a debilitating autoimmune condition characterized by limited therapeutic options. Dihydroartemisinin (DHA), an antimalarial compound, exhibits promising immunomodulatory effects against SLE; however, its clinical application is limited by poor bioavailability.</p> Methods <p>This study presented an innovative DHA delivery system based on macrophage membrane-coated nanoparticles (CCR2-MM@PEG-PCL/DHA), engineered to target SLE and its severe renal manifestation, lupus nephritis (LN). CCL2, a central mediator of leukocyte chemotaxis, contributes significantly to SLE pathogenesis. The targeting ability of nanoparticles to inflammatory sites is enhanced by genetically modifying the membrane of macrophages to over-express CCR2, and the nanoparticles can act as "nanobait" to capture CCL2 in the inflammatory microenvironment, thereby inhibiting macrophage-mediated inflammation. Efficacy was evaluated in vitro and in vivo using the MRL/lpr murine model.</p> Results <p>The findings showed that this nanosystem effectively alleviated symptoms in the MRL/lpr mouse model of SLE. Furthermore, CCR2-MM@PEG-PCL/DHA modulated the renal immune microenvironment by reducing monocyte/macrophage infiltration and reprogramming the M1/M2 macrophage balance, thus mitigating kidney damage in SLE mice.</p> Conclusions <p>The study establishes a mechanistically informed strategy for SLE intervention, substantiated by robust in vitro and in vivo data. These findings lay the foundation for translational research and potential clinical advancement in SLE therapy.</p>

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Engineered macrophage membrane-coated dihydroartemisinin nanoparticles with enhanced CCR2 expression improved symptoms in MRL/LPR mice by metabolic reprogramming of proinflammatory macrophages

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月2日

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  • Li Zhao,
  • Yanlong Zhang,
  • Rongrong Wang,
  • Jiaqi Yang,
  • Ruonan Wu,
  • Zewen Wu,
  • Jie Hu,
  • Shuqiu Zhang,
  • Liyun Zhang

摘要

Background

Systemic lupus erythematosus (SLE) is a debilitating autoimmune condition characterized by limited therapeutic options. Dihydroartemisinin (DHA), an antimalarial compound, exhibits promising immunomodulatory effects against SLE; however, its clinical application is limited by poor bioavailability.

Methods

This study presented an innovative DHA delivery system based on macrophage membrane-coated nanoparticles (CCR2-MM@PEG-PCL/DHA), engineered to target SLE and its severe renal manifestation, lupus nephritis (LN). CCL2, a central mediator of leukocyte chemotaxis, contributes significantly to SLE pathogenesis. The targeting ability of nanoparticles to inflammatory sites is enhanced by genetically modifying the membrane of macrophages to over-express CCR2, and the nanoparticles can act as "nanobait" to capture CCL2 in the inflammatory microenvironment, thereby inhibiting macrophage-mediated inflammation. Efficacy was evaluated in vitro and in vivo using the MRL/lpr murine model.

Results

The findings showed that this nanosystem effectively alleviated symptoms in the MRL/lpr mouse model of SLE. Furthermore, CCR2-MM@PEG-PCL/DHA modulated the renal immune microenvironment by reducing monocyte/macrophage infiltration and reprogramming the M1/M2 macrophage balance, thus mitigating kidney damage in SLE mice.

Conclusions

The study establishes a mechanistically informed strategy for SLE intervention, substantiated by robust in vitro and in vivo data. These findings lay the foundation for translational research and potential clinical advancement in SLE therapy.