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<p>Atherosclerosis serves as the pathological foundation for cardiovascular diseases, with sustained oxidative stress, chronic inflammation, and lipid accumulation being the key drivers of its progression. This study developed a novel pH-responsive nanoparticle, HEA@ML, with dual enzyme-mimicking properties and acid reactivity, designed to alleviate atherosclerosis. HEA@ML exhibited strong scavenging ability against reactive oxygen species (ROS) and demonstrated catalase (CAT) and superoxide dismutase (SOD) mimetic activities. The structure, comprising a FeCoNiZnMn high-entropy alloy core coated with a macrophage membrane fused with DOPE liposomes, facilitated targeted delivery to atherosclerotic lesions. In vitro experiments confirmed HEA@ML’s biocompatibility, effective macrophage internalization, and ability to reduce ROS production and alleviate mitochondrial dysfunction. The nanoparticle also modulated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, inhibited foam cell formation, and provides excellent T1-weighted magnetic resonance imaging (MRI) capability. Furthermore, HEA@ML demonstrated significant plaque reduction and stabilization in apoE-/- mice models. Biosafety studies confirmed clearance from major organs without serious side effects. These findings established HEA@ML as an effective, biocompatible therapeutic strategy with promising clinical translation potential for atherosclerosis treatment.</p> Graphical Abstract <p></p>

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PH-responsive biomimetic nanoparticle targeting the plaque microenvironment for diagnosis and synergistic treatment of atherosclerosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月4日

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  • Yusheng Qin,
  • Chao He,
  • ShanChen Feng,
  • Ziyi Wang,
  • Xiaoyue Nong,
  • Yingying Chen,
  • Jiaqian He,
  • Wei Zhang

摘要

Atherosclerosis serves as the pathological foundation for cardiovascular diseases, with sustained oxidative stress, chronic inflammation, and lipid accumulation being the key drivers of its progression. This study developed a novel pH-responsive nanoparticle, HEA@ML, with dual enzyme-mimicking properties and acid reactivity, designed to alleviate atherosclerosis. HEA@ML exhibited strong scavenging ability against reactive oxygen species (ROS) and demonstrated catalase (CAT) and superoxide dismutase (SOD) mimetic activities. The structure, comprising a FeCoNiZnMn high-entropy alloy core coated with a macrophage membrane fused with DOPE liposomes, facilitated targeted delivery to atherosclerotic lesions. In vitro experiments confirmed HEA@ML’s biocompatibility, effective macrophage internalization, and ability to reduce ROS production and alleviate mitochondrial dysfunction. The nanoparticle also modulated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, inhibited foam cell formation, and provides excellent T1-weighted magnetic resonance imaging (MRI) capability. Furthermore, HEA@ML demonstrated significant plaque reduction and stabilization in apoE-/- mice models. Biosafety studies confirmed clearance from major organs without serious side effects. These findings established HEA@ML as an effective, biocompatible therapeutic strategy with promising clinical translation potential for atherosclerosis treatment.

Graphical Abstract