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首页> 外文期刊>Journal of Controlled Release: Official Journal of the Controlled Release Society >Ginsenoside Rg3-loaded, reactive oxygen species-responsive polymeric nanoparticles for alleviating myocardial ischemia-reperfusion injury
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Ginsenoside Rg3-loaded, reactive oxygen species-responsive polymeric nanoparticles for alleviating myocardial ischemia-reperfusion injury

机译：用于减轻心肌缺血再灌注损伤的人参皂苷RG3加载的反应性氧物质响应性聚合物纳米颗粒

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摘要

Myocardial ischemia-reperfusion injury (MIRI) is a serious threat to the health and lives of patients without any effective therapy. Excessive production of reactive oxygen species (ROS) is considered a principal cause of MIRI. Some natural products, including ginsenoside Rg3 (Rg3), exhibit robust antioxidant activity. However, the lack of an effective delivery strategy for this hydrophobic compound hinders its clinical application. In addition, therapeutic targets and molecular mechanisms of Rg3 require further elucidation to establish its mode of action. This study aimed to generate ROS-responsive nanoparticles (PEG-b-PPS) via the self-assembly of diblock copolymers of poly (ethylene glycol) (PEG) and poly (propylene sulfide) (PPS) and use them for Rg3 encapsulation and delivery. We identified FoxO3a as the therapeutic target of Rg3 using molecular docking and gene silencing. In rat ischemia-reperfusion model, an intramyocardial injection of Rg3-loaded PEG-b-PPS nanoparticles improved the cardiac function and reduced the infarct size. The mechanism of action was established as Rg3 targeting of FoxO3a, which inhibited the promotion of oxidative stress, inflammation, and fibrosis via downstream signaling pathways. In conclusion, this approach, involving ROS-responsive drug release, together with the identification of the target and mechanism of action of Rg3, provided an effective strategy for treating ischemic diseases and oxidative stress and could accelerate the implementation of hydrophobic natural products in clinical applications.
机译：心肌缺血再灌注损伤（MIRI）对没有任何有效治疗的患者的健康和生活是严重的威胁。过度生产反应性氧（ROS）被认为是MIRI的主要原因。一些天然产品，包括人参皂苷RG3（RG3），具有稳健的抗氧化活性。然而，缺乏这种疏水化合物的有效交付策略阻碍了其临床应用。此外，RG3的治疗靶标和分子机制需要进一步阐明以建立其作用方式。该研究旨在通过聚（乙二醇）（PEG）和聚（硫化丙酯）（PPS）的二嵌段共聚物的自组装产生ROS响应纳米颗粒（PEG-B-PP），并使用它们进行RG3封装和递送。我们使用分子对接和基因沉默将FOXO3A鉴定为RG3的治疗靶标。在大鼠缺血再灌注模型中，Intramyard注射RG3负载的PEG-B-PPS纳米粒子改善了心脏功能并降低了梗塞尺寸。将作用机制建立为FOXO3A的RG3靶向，其抑制通过下游信号通路促进氧化应激，炎症和纤维化。总之，这种方法，涉及ROS-enverysive药物释放，以及RG3的靶向和作用机制，提供了治疗缺血性疾病和氧化应激的有效策略，可以加速临床应用中疏水性天然产物的实施。

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