pH/ROS-responsive propelled nanomotors for the active treatment of renal injury

Abstract

Effective drugs that can be quickly delivered to and retained for a long time in the renal tubule are necessary for acute kidney injury (AKI) treatment. In this study, a gold nanoparticle-modified mesoporous silica (Au@MSN-NH₂)-camouflaged (methoxyphenyl)(morpholino)phosphinodithioic acid (GYY4137) asymmetrical nanosystem decorated with L-serine (S; an AKI-targeting agent) and D-Arg-dimethylTyr-Lys-Phe-NH₂ (TK-SS31; a reactive oxygen species (ROS)-sensitive thioketal linker/mitochondria-targeted antioxidant) was constructed for the treatment of renal tubule and mitochondrial injury as well as the synergistic and active treatment of AKI. Due to the enhanced permeability and retention (EPR) of nanomotors, they could progressively accumulate in renal sites. The asymmetrical nanosystem achieved effective drug distribution in the kidney as well as pH-responsive hydrogen sulfide (H₂S) release and ROS-responsive SS31 release, resulting in an active therapeutic effect mediated by nanomotor motion resulting from asymmetrical H₂S release.