ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule.

ABSTRACT: 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

SUBMITTER: Liu D 

PROVIDER: S-EPMC7546709 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature