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中性粒细胞介导的纳米酶输送系统用于急性损伤治疗
Yu Yang1,2, Jiang Du3, Jingjing Gan4
1Department of Andrology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210008, China.
Advanced healthcare materials
|June 20, 2024
概括
这项研究引入了一种中性粒细胞介导的纳米酶输送系统,用于治疗急性损伤 (AKI). 这种创新方法克服了膜过障碍,显示了AKI治疗的重大前景.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 腎臟醫學 腎臟醫學
背景情况:
- 在急性损伤 (AKI) 中,纳米酶对清除反应性氧物种 (ROS) 具有前景.
- 淋巴膜过屏障 (GFB) 限制了纳米酶向脏的输送.
- 需要有针对性的传递系统来克服GFB的局限性,以获得有效的AKI治疗.
研究的目的:
- 为纳米酶开发一种中性粒细胞介导的输送系统,以向AKI的炎症脏.
- 利用cRGD-脂质体 (cRGD-LPs) 通过中性粒细胞进行增强的纳米酶运输,向整合素αvβ1.
- 为了评估该系统在治疗因胰岛素缺血-再输血 (I/R) 诱导的AKI中的疗效.
主要方法:
- 开发了纳米酶载的cRGD脂质体,并将其封装在脂质体内.
- 中性粒细胞被劫持,以运输纳米酶载荷的脂质体到炎症的脏组织.
- 该系统的抗氧化和抗亡作用在体外 (HK-2,NRK-52E细胞) 和体内 (I/R诱导的AKI小鼠) 进行了评估.
- 分析了Nrf2核转位和HO-1表达的变化,以了解作用机制.
主要成果:
- 中性粒细胞介导的输送系统在细胞系中表现出显著的抗氧化和抗亡能力.
- 在AKI小鼠中,单剂量LM@cRGD-LPs减少了功能指标和病理损伤.
- 治疗抑制了管细胞亡,并减少了管损伤标志物的表达.
- 从机制上讲,LM@cRGD-LPs抑制了Nrf2核转位和HO-1表达,使脏Nrf2水平增加了99.51%,HO-1降低了86.31%.
结论:
- 中性粒细胞介导的纳米酶传递有效地向炎症脏,克服了AKI治疗的GFB限制.
- 这种策略通过减少损伤,抑制亡和调节关键分子通路,显示出显著的治疗潜力.
- 开发的系统有望治疗AKI和其他炎症性疾病.
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