Scholarlink

<p>Asthma is a chronic inflammatory respiratory disease worldwide. Its severe phenotypes, particularly the glucocorticoid-resistant ones, pose a major challenge, with neutrophilic inflammation being the key driver. However, no effective treatments are currently available. Herein, we report a macromolecular therapeutic strategy capable of targeting multiple key cells involved in the pathogenesis of neutrophilic asthma. The macromolecular therapy named PMART is constructed by conjugating artesunate and polyethylene glycol to the triazine scaffold. It is highly water-soluble and can self-assemble into nanomicelles, which enables efficient targeting to inflamed lung tissues and localization in inflammatory cells. In a murine model of neutrophilic asthma, PMART has proven to have in vivo efficacy equivalent to or greater than that of two clinically used anti-asthma drugs. Mechanistically, PMART reduces succinate levels by inhibiting branched-chain amino acid transaminase 1 (BCAT1) overexpression, thereby suppressing neutrophilic inflammation via blocking the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and the production of pro-inflammatory cytokines. Notably, PMART exhibits a favorable safety profile in mice. Taken together, these data support the potential of PMART as a novel and highly effective therapeutic agent for neutrophilic asthma and other neutrophil-mediated 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

Artesunate-based macromolecular therapy attenuates neutrophilic asthma by targeting the BCAT1/Succinate/NLRP3 metabolite-immunity cascade

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月3日

查看全文
  • Jing Gong,
  • Min Zhou,
  • Yue Huang,
  • Mengjun Yu,
  • Qiang Zhou,
  • Shiwen Chen,
  • Jia Wang,
  • Min Yang,
  • Qing Luo,
  • Rong Zhang,
  • Jingbin Huang

摘要

Asthma is a chronic inflammatory respiratory disease worldwide. Its severe phenotypes, particularly the glucocorticoid-resistant ones, pose a major challenge, with neutrophilic inflammation being the key driver. However, no effective treatments are currently available. Herein, we report a macromolecular therapeutic strategy capable of targeting multiple key cells involved in the pathogenesis of neutrophilic asthma. The macromolecular therapy named PMART is constructed by conjugating artesunate and polyethylene glycol to the triazine scaffold. It is highly water-soluble and can self-assemble into nanomicelles, which enables efficient targeting to inflamed lung tissues and localization in inflammatory cells. In a murine model of neutrophilic asthma, PMART has proven to have in vivo efficacy equivalent to or greater than that of two clinically used anti-asthma drugs. Mechanistically, PMART reduces succinate levels by inhibiting branched-chain amino acid transaminase 1 (BCAT1) overexpression, thereby suppressing neutrophilic inflammation via blocking the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and the production of pro-inflammatory cytokines. Notably, PMART exhibits a favorable safety profile in mice. Taken together, these data support the potential of PMART as a novel and highly effective therapeutic agent for neutrophilic asthma and other neutrophil-mediated diseases.

Graphical Abstract