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Journal of controlled release : official journal of the Controlled Release Society. 2025 Jun 10:113950. doi: 10.1016/j.jconrel.2025.113950 Q111.52025

Targeting ferroptosis and mitophagy with neutrophil-inspired nanozyme for Parkinson's disease therapy

灵感启发的纳米酶靶向铁死亡和线粒体自噬治疗帕金森病 翻译改进

Yu Tian  1, Feng Wang  1, Jing Ma  1, Wei Huang  1, Xiaodan Zhang  1, Chengzhong Du  1, Penghui Wei  1, Wen Huang  1, Yang Zhu  2, Yuanxiang Lin  3

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作者单位

  • 1 Department of Neurosurgery, Neurosurgery Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
  • 2 Department of Neurosurgery, Neurosurgery Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China. Electronic address: zhuyang@mail.ustc.edu.cn.
  • 3 Department of Neurosurgery, Neurosurgery Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China. Electronic address: lyx99070@163.com.

    • DOI: 10.1016/j.jconrel.2025.113950 PMID: 40505893

    摘要 中英对照阅读

    Parkinson's disease (PD) is characterized by neurodegeneration, oxidative stress, and α-synuclein aggregation. While L-DOPA provides symptomatic relief through dopamine replenishment, it lacks neuroprotective effects and fails to address oxidative stress, iron dysregulation, and protein aggregation underlying PD pathogenesis. The development of antioxidant enzymes shows promise, yet challenges persist in blood-brain barrier (BBB) penetration and effectiv... ...点击完成人机验证后继续浏览

    帕金森病（PD）的特征是神经退行性变、氧化应激和α-突触核蛋白聚集。虽然左旋多巴通过补充多巴胺提供症状缓解，但它缺乏神经保护作用，并且无法解决导致PD发病机制的氧化应激、铁调节异常以及蛋白质聚集问题。开发抗氧化酶显示出前景，但仍然存在如何穿透血脑屏障（BBB）和有效减轻神经炎症等方面的挑战。我们的初步研究发现，Icariside II (ICS II) 与 Fe3+ 协同作用可以促进形成具有增强的抗氧化能力和铁螯合作用的自组装金属-多酚纳米酶(Fe-Ic)。基于这一发现，我们通过合理的设计策略开发了包裹中性粒细胞膜的纳米酶（R-NM@Fe-Ic），并对其进行DSPE-PEG-RVG29修饰，以同时针对PD中的铁调节异常和铁死亡，实现对神经炎症区域的目标递送。R-NM@Fe-Ic表现出双酶活性，减少α-突触核蛋白聚集、抑制脂质过氧化，并增加谷胱甘肽过氧化物酶4的表达，从而比左旋多巴更有效地防止神经元铁死亡。此外，它还促进了线粒体自噬，抑制了有毒蛋白质聚集并减轻了神经炎症。体内研究表明，R-NM@Fe-Ic能够有效穿透BBB并在PD受影响的大脑区域积聚。行为分析显示，在运动功能、自发活动和认知表现方面均显著改善，并且在症状管理和神经保护方面优于左旋多巴。这项研究建立了一个新的仿生纳米酶平台，并提供了同时针对铁死亡和增强线粒体自噬途径在神经炎症障碍中治疗潜力的见解。

    关键词：铁死亡；纳米酶；神经炎症；中性粒细胞膜；帕金森病。

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    期刊名：Journal of controlled release

    缩写：J CONTROL RELEASE

    ISSN：0168-3659

    e-ISSN：1873-4995

    IF/分区：11.5/Q1

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    Targeting ferroptosis and mitophagy with neutrophil-inspired nanozyme for Parkinson's disease therapy