Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Nano Lett. 2021 May 26;21(10):4394-4402. doi: 10.1021/acs.nanolett.1c01044. Epub 2021 May 17.
The high demand for acute kidney injury (AKI) therapy calls the development of multifunctional nanomedicine for renal management with programmable pharmacokinetics. Here, we developed a renal-accumulating DNA nanodevice with exclusive kidney retention for longitudinal protection of AKI in different stages in a renal ischemia-reperfusion (I/R) model. Due to the prolonged kidney retention time (>12 h), the ROS-sensitive nucleic acids of the nanodevice could effectively alleviate oxidative stress by scavenging ROS in stage I, and then the anticomplement component 5a (aC5a) aptamer loaded nanodevice could sequentially suppress the inflammatory responses by blocking C5a in stage II, which is directly related to the cytokine storm. This sequential therapy provides durable and pathogenic treatment of kidney dysfunction based on successive pathophysiological events induced by I/R, which holds great promise for renal management and the suppression of the cytokine storm in more broad settings including COVID-19.
急性肾损伤 (AKI) 治疗的高需求促使人们开发具有可编程药代动力学的多功能纳米医学，以进行肾脏管理。在这里，我们开发了一种具有肾脏蓄积特性的 DNA 纳米器件，该纳米器件具有独特的肾脏保留特性，可在肾缺血再灌注 (I/R) 模型的不同阶段对 AKI 进行纵向保护。由于其在肾脏中的保留时间延长 (>12 h)，纳米器件中的 ROS 敏感核酸可以通过清除 I 期的 ROS 有效缓解氧化应激，然后负载 aC5a 适体的纳米器件可以通过阻断 II 期的 C5a 来抑制炎症反应，这与细胞因子风暴直接相关。这种序贯治疗为基于 I/R 诱导的连续病理生理事件的肾脏功能障碍提供了持久且针对性的治疗，这为肾脏管理以及在包括 COVID-19 在内的更广泛环境中抑制细胞因子风暴提供了巨大的希望。
