Scholarlink

<p>Rheumatoid arthritis (RA), a chronic and debilitating autoimmune inflammatory disease, is critically driven by macrophages within the inflamed synovium. The inflammatory cascade is sustained by a synergistic imbalance between macrophage pyroptosis and metabolic dysfunction, resulting in the formation of a dual barrier to effective intervention. GSDME-targeted siRNA delivery effectively blocks pyroptosis; however, uncorrected metabolic defects leave “saved” macrophages in a proinflammatory state, thereby aggravating RA. To address this “dual dilemma”, folic acid-modified macrophage membrane–lipid hybrid nanoparticles (FA-MMLNPs) were engineered for spatiotemporally coordinated codelivery of GSDME siRNA (siG) and 4-octyl itaconate (4-OI). The biomimetic membrane promotes inflammatory homing, folic acid enhances FR-positive macrophage endocytosis, and the lipid core protects the siRNA and ensures synchronous release. Mechanistically, SiG inhibits pyroptosis, whereas 4-OI restores mitochondrial metabolism to reprogram macrophages to an anti-inflammatory phenotype. This integrated material platform organically combines pathway-specific gene silencing, metabolic correction, and precise biointerface engineering, providing a versatile paradigm for material design in RA and other inflammation-driven diseases.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Biomimetic hybrid nanoparticles for dual regulation of macrophage pyroptosis and metabolism in rheumatoid arthritis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月8日

查看全文
  • Guang Yang,
  • Lingxiao Xu,
  • Ruijie Zhang,
  • Zhenyu Zhu,
  • Kelei Wang,
  • Kaipeng Jin,
  • Yifan Wu,
  • Hanxu Huang,
  • Jiaxuan Zou,
  • Wushi Cui,
  • Xiaohua Yu,
  • Lingling Sun,
  • Zhenxuan Shao

摘要

Rheumatoid arthritis (RA), a chronic and debilitating autoimmune inflammatory disease, is critically driven by macrophages within the inflamed synovium. The inflammatory cascade is sustained by a synergistic imbalance between macrophage pyroptosis and metabolic dysfunction, resulting in the formation of a dual barrier to effective intervention. GSDME-targeted siRNA delivery effectively blocks pyroptosis; however, uncorrected metabolic defects leave “saved” macrophages in a proinflammatory state, thereby aggravating RA. To address this “dual dilemma”, folic acid-modified macrophage membrane–lipid hybrid nanoparticles (FA-MMLNPs) were engineered for spatiotemporally coordinated codelivery of GSDME siRNA (siG) and 4-octyl itaconate (4-OI). The biomimetic membrane promotes inflammatory homing, folic acid enhances FR-positive macrophage endocytosis, and the lipid core protects the siRNA and ensures synchronous release. Mechanistically, SiG inhibits pyroptosis, whereas 4-OI restores mitochondrial metabolism to reprogram macrophages to an anti-inflammatory phenotype. This integrated material platform organically combines pathway-specific gene silencing, metabolic correction, and precise biointerface engineering, providing a versatile paradigm for material design in RA and other inflammation-driven diseases.

Graphical Abstract