%0 Journal Article %A Liu, Di %A Shu, Gaofeng %A Jin, Feiyang %A Qi, Jing %A Xu, Xiaoling %A Du, Yan %A Yu, Hui %A Wang, Jun %A Sun, Mingchen %A You, Yuchan %A Zhu, Minxia %A Chen, Meixuan %A Zhu, Luwen %A Shen, Qiying %A Ying, Xiaoying %A Lou, Xuefang %A Jiang, Saiping %A Du, Yongzhong %T ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule %D 2020 %R 10.1126/sciadv.abb7422 %J Science Advances %P eabb7422 %V 6 %N 41 %X The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine–modified chitosan (SC) was synthesized as a potential AKI kidney–targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule–1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion–induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)–sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis. %U https://advances.sciencemag.org/content/advances/6/41/eabb7422.full.pdf