A Strontium-Based Polyphenol Nanozyme Reverses Cisplatin-Related Acute Kidney Injury Through Near-Infrared-Enhanced PI3K/AKT Pathway Inhibition and Macrophage M2 Directional Polarization

en This link goes to a English section zh This link goes to a Chinese section Cisplatin-related acute kidney injury (CP-AKI) is a serious complication of cisplatin (CP) treated patients with cancer with high morbidity and mortality rates. It is directly related to the abnormal accumulation of CP in renal tubular epithelial cells, causing metabolic toxicity, DNA damage, and oxidative stress. Herein, we developed a polyphenol nanozyme (SrEG) by the coordination of strontium ions (Sr 2+ ) and epigallocatechin gallate. It was demonstrated that SrEG, combined with NIR irradiation, exhibited excellent capabilities of scavenging various types of reactive oxygen species (ROS). It was also determined that SrEG + NIR efficiently eliminated intracellular ROS levels, inhibited inflammation related cytokines expression, and induced macrophage M2 directional polarization, thus preventing cellular damage. By intravenous (IV) administration, SrEG was efficiently accumulated in the kidney and gradually degraded. Accordingly, the administration of SrEG + NIR offered the perfect therapeutic effects in CP-AKI rats by inhibiting the PI3K/AKT pathway, thus accelerating kidney function repair. Overall, the strategy of SrEG + NIR showed substantial clinical promise as a potential therapeutic strategy in ROS-related diseases. 摘要 en This link goes to a English section zh This link goes to a Chinese section 顺铂相关的急性肾损伤(CP-AKI)是癌症患者进行顺铂(CP)治疗时的严重并发症,具有较高的致病率和死亡率。CP-AKI与CP在肾小管上皮细胞中的异常积聚直接相关,从而导致代谢毒性、DNA损伤和氧化应激。在此,我们通过锶离子(Sr 2+ )和表没食子儿茶素没食子酸酯的配位开发了一种多酚纳米酶(SrEG)。结果表明,SrEG结合近红外光照展现出优异的清除各种类型活性氧(ROS)的能力。而且SrEG + NIR有效地降低细胞内ROS水平,抑制炎症相关因子的表达,并诱导巨噬细胞M2定向极化,从而防止细胞损伤。通过静脉注射(IV)给药,SrEG在肾脏中有效积聚并逐渐降解。因此,SrEG + NIR的治疗策略通过抑制PI3K/AKT通路,从而加速肾功能修复,为CP-AKI大鼠提供了完美的治疗效果。总体而言,SrEG + NIR作为ROS相关疾病的潜在治疗策略显示出巨大的临床前景。