Related Experiment Video
Updated: Jul 8, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
Cross-Linked Diselenide Nanovesicles against Acute Liver Injury by Seamless Integration of ROS Elimination and Source
Shaoxiong Zhang1,2, Dongli Wang1, Qian Liu2
1National Engineering Research Center for Biomaterials and College of Biomedical Engineering, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China.
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.
Insights
A novel nanovesicle therapy (FA@cSeLAV) combats acute liver injury by scavenging reactive oxygen species (ROS) and inhibiting their endogenous production. This dual action offers superior anti-inflammatory effects compared to current treatments.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Hepatology
Background:
- Acute liver injury (ALI) presents a growing clinical challenge with limited effective treatments.
- Current therapies for ALI focus on reactive oxygen species (ROS) scavenging but neglect endogenous ROS production, limiting efficacy.
- Hepatic macrophages are key mediators of ROS-driven damage in ALI.
Purpose of the Study:
- To develop a novel nanovesicle system for synergistic ROS regulation in ALI.
- To investigate the dual-action mechanism of inhibiting endogenous ROS production and scavenging extracellular ROS.
- To evaluate the therapeutic potential of FA@cSeLAV in ALI models.
Main Methods:
- Fabrication of cross-linked diselenide nanovesicles with folic acid modification (FA@cSeLAV).
- Assessment of FA@cSeLAV's ability to scavenge ROS and inhibit endogenous ROS production via mitochondrial tricarboxylic acid (TCA) cycle interference.
- In vivo evaluation of FA@cSeLAV's anti-inflammatory efficacy in ALI models, comparing it with N-acetylcysteine (NAC).
Main Results:
- FA@cSeLAV effectively targets hepatic macrophages and scavenges excessive ROS.
- The nanovesicles depolymerize to selenolipoic acid (DSeO2LA), which inhibits mitochondrial TCA cycle enzymes, reducing aberrant ROS production.
- FA@cSeLAV demonstrated superior anti-inflammatory effects in ALI compared to NAC, maintaining ROS levels within the normal hepatic range.
Conclusions:
- FA@cSeLAV offers a novel synergistic strategy for sustained ROS regulation in ALI.
- The dual-action mechanism addresses limitations of current ROS-scavenging therapies.
- This approach holds promise for treating inflammation-associated diseases, including ALI.
