State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, Anhui, P. R. China.
ACS Appl Mater Interfaces. 2023 May 10;15(18):21854-21865. doi: 10.1021/acsami.3c00714. Epub 2023 Apr 28.
Chemotherapeutic drug-induced acute kidney injury (AKI) involves pathologically increased labile iron species in the kidneys that mediate the excessive generation of reactive oxygen species (ROS) to induce ferroptosis and apoptosis, subsequently driving renal dysfunction. Herein, we report renal clearable quantum dot-drug conjugates (QDCs) composed of carbon quantum dot (CDs), deferoxamine (DFO), and poly(ethylene glycol) (PEG) for attenuating chemotherapeutic drug-induced AKI. The CDs component in QDCs can not only provide DFO with high renal specificity to effectively remove the pathological labile iron species in the kidneys to block the source of ROS generation but also exert high antioxidative effects to avoid renal oxidative damage caused by the ROS that have been overproduced. In cisplatin-induced AKI mice, QDCs can inhibit ferroptosis and apoptosis with high efficacy for AKI treatment. This study will provide a new paradigm to realize enhanced therapeutic efficacy for AKI by simultaneously removing the pathological labile iron species and eliminating overproduced ROS in the kidneys to achieve the goal of addressing both symptoms and root causes.
化疗药物诱导的急性肾损伤（AKI）涉及肾脏中病理上增加的不稳定铁物种，这些铁物种介导活性氧（ROS）的过度生成，从而诱导铁死亡和细胞凋亡，进而导致肾功能障碍。在此，我们报告了由碳量子点（CDs）、去铁胺（DFO）和聚乙二醇（PEG）组成的肾脏可清除的量子点-药物偶联物（QDCs），用于减轻化疗药物诱导的 AKI。QDCs 中的 CDs 成分不仅可以为 DFO 提供高肾特异性，以有效去除肾脏中病理上的不稳定铁物种，从而阻断 ROS 生成的源头，还可以发挥高抗氧化作用，避免由过度生成的 ROS 引起的肾脏氧化损伤。在顺铂诱导的 AKI 小鼠中，QDCs 可以高效抑制铁死亡和细胞凋亡，从而有效治疗 AKI。本研究将为通过同时去除肾脏中的病理不稳定铁物种和消除过度生成的 ROS 来实现增强 AKI 的治疗效果提供一个新范例，从而达到治标又治本的目的。
