RT Journal Article
SR Electronic
T1 ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabb7422
DO 10.1126/sciadv.abb7422
VO 6
IS 41
A1 Liu, Di
A1 Shu, Gaofeng
A1 Jin, Feiyang
A1 Qi, Jing
A1 Xu, Xiaoling
A1 Du, Yan
A1 Yu, Hui
A1 Wang, Jun
A1 Sun, Mingchen
A1 You, Yuchan
A1 Zhu, Minxia
A1 Chen, Meixuan
A1 Zhu, Luwen
A1 Shen, Qiying
A1 Ying, Xiaoying
A1 Lou, Xuefang
A1 Jiang, Saiping
A1 Du, Yongzhong
YR 2020
UL http://advances.sciencemag.org/content/6/41/eabb7422.abstract
AB 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.