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SOD 矿化沸石咪唑骨架-8 治疗化疗相关急性肾损伤。

SOD mineralized zeolitic imidazole framework-8 for the treatment of chemotherapy-related acute kidney injury.

机构信息

Department of Urology, First Hospital of Jilin University, Changchun, PR China; Department of Radiology, First Hospital of Jilin University, Changchun, PR China.

Department of Radiology, First Hospital of Jilin University, Changchun, PR China.

出版信息

Colloids Surf B Biointerfaces. 2023 Sep;229:113447. doi: 10.1016/j.colsurfb.2023.113447. Epub 2023 Jul 21.

Abstract

Acute kidney injury (AKI), a prevalent and fatal adverse event, seriously affects cancer patients undergoing chemotherapy. The most important pathological mechanism of AKI is oxidative stress from reactive oxygen species (ROS). Currently, ROS scavenging is a promising strategy to manage the risk of chemotherapy-induced AKI. Herein, we successfully synthesized SOD@ZIF-8 nanoparticles by biomimetic mineralization, which were taken up by cells and could improve cell viability by limiting oxidative stress damage, as found in in vitro studies. Moreover, SOD@ZIF-8 nanoparticles exhibit broad-spectrum antioxidant properties in addition to significant renal accumulation in AKI mice, preventing clinically related cisplatin-induced AKI in murine models. AKI alleviation in the model was validated by measuring blood serum, staining kidney tissue, and related biomarkers. SOD@ZIF-8 nanoparticle therapeutic efficiency exceeds NAC, a small molecular antioxidant functioning through free radical scavenging. The results suggest SOD@ZIF-8 nanoparticles as a potential therapeutic option for AKI and other ROS-related disorders.

摘要

急性肾损伤 (AKI) 是一种常见且致命的不良事件,严重影响接受化疗的癌症患者。AKI 的最重要病理机制是活性氧 (ROS) 引起的氧化应激。目前,清除 ROS 是管理化疗引起的 AKI 风险的一种有前途的策略。在此,我们通过仿生矿化成功合成了 SOD@ZIF-8 纳米粒子,在体外研究中发现,这些纳米粒子被细胞摄取后,通过限制氧化应激损伤来提高细胞活力。此外,SOD@ZIF-8 纳米粒子除了在 AKI 小鼠中具有显著的肾脏积累外,还具有广谱的抗氧化特性,可预防临床相关顺铂诱导的 AKI 。通过测量血清、肾脏组织染色和相关生物标志物来验证模型中的 AKI 缓解情况。SOD@ZIF-8 纳米粒子的治疗效率超过 NAC,NAC 是一种通过自由基清除作用发挥作用的小分子抗氧化剂。结果表明 SOD@ZIF-8 纳米粒子是 AKI 和其他与 ROS 相关疾病的潜在治疗选择。

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