Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology Nanjing University, No. 321 Zhongshan Road, Nanjing 210008, Jiangsu, China.
School of Chemistry & Chemical Engineering, Nanjing University, No. 163 Xianlin Road, Nanjing 210008, Jiangsu, China.
ACS Appl Mater Interfaces. 2020 Jul 15;12(28):31745-31756. doi: 10.1021/acsami.0c05041. Epub 2020 Jul 2.
As a reactive oxygen species (ROS)-promoted disease, acute kidney injury (AKI) is associated with high mortality and morbidity, but no effective pharmacological treatment is available. Kidney-targeted and ROS-reactive antioxidants are in urgent demand for AKI treatment. A promising nanotechnology-based strategy for targeting renal tubules offers new perspectives for AKI treatment but remains challenging because of the glomerular filtration barrier, which requires ultrasmall-sized therapeutics for penetration and filtration. Here, we fabricated four potential antioxidative carbon nanodots (CNDs) with ultrasmall size. After balancing the antioxidant properties and biocompatibility, -phenylenediamine-based CNDs (PDA-CNDs) were chosen for further research. PDA-CNDs demonstrated remarkable antioxidant properties for scavenging multiple toxic free radicals, enabling efficient protection of cells under various oxidative stresses in vitro. Moreover, fluorescence imaging revealed that PDA-CNDs preferentially accumulated in the injured kidney of mice with ischemia-reperfusion (IR)-induced AKI. Blood renal function tests and kidney tissue staining revealed the therapeutic efficacy of PDA-CNDs for AKI in both the murine IR-induced AKI model and cisplatin-induced AKI model. Collectively, this is the first study revealing that specific rationally designed CNDs could be a promising pharmacological treatment for AKI induced by ROS.
作为一种活性氧（ROS）引发的疾病，急性肾损伤（AKI）与高死亡率和高发病率相关，但目前尚无有效的药物治疗方法。针对 AKI 治疗，急需具有肾脏靶向性和 ROS 反应性的抗氧化剂。一种有前途的基于纳米技术的靶向肾小管的策略为 AKI 治疗提供了新的视角，但由于肾小球滤过屏障的存在，这仍然具有挑战性，因为该屏障需要超小尺寸的治疗药物才能穿透和过滤。在这里，我们制备了四种具有超小尺寸的潜在抗氧化性碳纳米点（CND）。在平衡抗氧化性能和生物相容性后，选择基于 -苯二胺的 CND（PDA-CND）进行进一步研究。PDA-CND 具有显著的清除多种毒性自由基的抗氧化性能，能够在体外各种氧化应激条件下有效保护细胞。此外，荧光成像显示 PDA-CND 优先积聚在缺血再灌注（IR）诱导的 AKI 小鼠的受损肾脏中。血液肾功能测试和肾脏组织染色显示 PDA-CND 在小鼠 IR 诱导的 AKI 模型和顺铂诱导的 AKI 模型中均具有治疗 AKI 的功效。总之，这是第一项揭示特定合理设计的 CND 可能成为 ROS 诱导的 AKI 的一种有前途的药物治疗方法的研究。
