Cross-Linked Diselenide Nanovesicles against Acute Liver Injury by Seamless Integration of ROS Elimination and Source Inhibition.
TL;DR
This work introduces a cross-linked diselenide nanovesicles with surface folic acid modification (FA@cSeLAV), which effectively targets hepatic macrophages, key mediators of ROS-driven damage in ALI, and seamlessly integrates symptomatic-level ROS elimination with the inhibition of endogenous ROS production.
Abstract
The persistent rise in case incidence and the acute shortage of effective treatments have heightened the urgent need for robust strategies to combat acute liver injury (ALI). Targeting reactive oxygen species (ROS) scavenging remains the predominant therapeutic approach. However, current clinical interventions and emerging therapies primarily emphasize symptomatic-level ROS elimination while neglecting endogenous ROS production inhibition, which severely limits their therapeutic efficiency. Herein, we introduce a cross-linked diselenide nanovesicles with surface folic acid modification (FA@cSeLAV), which effectively targets hepatic macrophages, key mediators of ROS-driven damage in ALI, and seamlessly integrates symptomatic-level ROS elimination with the inhibition of endogenous ROS production. Briefly, diselenide-enriched FA@cSeLAV efficiently scavenges excessive ROS and undergoes depolymerization to predominantly form the oxidized monomer selenolipoic acid (DSeO2LA). Seamlessly, DSeO2LA impairs the mitochondrial tricarboxylic acid (TCA) cycle by inhibiting the acyl group transfer activity of key mitochondrial metabolic enzymes, thus interfering with mitochondrial energy metabolism and suppressing aberrant ROS production. Impressively, this internal-external synergistic strategy maintains sustained and robust ROS regulation at normal levels within the hepatic environment, significantly surpassing the anti-inflammatory efficiency of approved drug N-acetylcysteine (NAC), offering insights for the clinical treatment of inflammation-associated diseases.