Related Experiment Video
Updated: May 12, 2026
Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Acid responsive molybdenum (Mo)-based nanoparticles inhibit the cGAS-STING signaling pathway for sepsis therapy
Xinyu Wang1,2, Qingbin He2, Lining Wang3
1Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
Abstract:
Sepsis, an inflammatory disease caused by bacterial infection, has become a global public health crisis. Excessive reactive oxygen species (ROS) in sepsis patients act as the primary trigger for activating intracellular immune pathways, ultimately leading to multiple organ dysfunction syndrome. The overexpression of acidic metabolites and ROS, characteristic of the infected microenvironment, significantly impedes sepsis treatment. Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, plays a key role in inflammatory diseases. The detrimental effects of STING in sepsis have been well documented. Here, we developed a pH-responsive nanotherapy platform (DMSNM@C-178/PAA) that combines ROS scavenging with cGAS-STING pathway inhibition for anti-inflammatory therapy. This nanoparticle is selectively released in the infected microenvironment, where reduced molybdenum-based polyoxometalates (Mo-POM) efficiently neutralize toxic ROS in vivo, while C-178 selectively inhibits the cGAS-STING pathway, thereby attenuating the inflammatory response and preventing organ deterioration. In vitro and in vivo studies demonstrate that DMSNM@C-178/PAA treats sepsis by eliminating excess ROS and modulating autoimmune dysfunction via the cGAS-STING pathway, providing a novel therapeutic strategy for sepsis management.
Insights
This study introduces a novel nanotherapy for sepsis, combining reactive oxygen species (ROS) scavenging and cGAS-STING pathway inhibition. The therapy effectively reduces inflammation and prevents organ damage in sepsis patients.
Area of Science:
- Biomedical Engineering
- Immunology
- Nanomedicine
Background:
- Sepsis is a critical global health issue driven by bacterial infections and characterized by excessive reactive oxygen species (ROS).
- The overproduction of ROS and acidic metabolites in the infected microenvironment hinders effective sepsis treatment.
- The cyclic GMP-AMP synthase (cGAS)-STING pathway is a key player in inflammatory responses during sepsis.
Purpose of the Study:
- To develop a pH-responsive nanotherapy platform for targeted anti-inflammatory treatment of sepsis.
- To combine ROS scavenging with cGAS-STING pathway inhibition within a single therapeutic agent.
Main Methods:
- Development of a pH-responsive nanoparticle (DMSNM@C-178/PAA) encapsulating reduced molybdenum-based polyoxometalates (Mo-POM) and C-178.
- Selective release of the nanotherapy in the acidic infected microenvironment.
- Evaluation of ROS neutralization and cGAS-STING pathway inhibition in vitro and in vivo.
Main Results:
- The nanotherapy selectively targets the infected microenvironment, releasing Mo-POM to scavenge ROS and C-178 to inhibit the cGAS-STING pathway.
- Demonstrated efficient neutralization of excess ROS and modulation of the cGAS-STING pathway.
- Prevented organ deterioration associated with sepsis progression.
Conclusions:
- DMSNM@C-178/PAA offers a novel therapeutic strategy for sepsis management by addressing both ROS overproduction and cGAS-STING-mediated inflammation.
- The pH-responsive nanotherapy platform shows potential for treating sepsis and preventing multiple organ dysfunction syndrome.
Related Concept Videos
01:28Gene Regulation in Microbial Communities: Quorum Sensing
01:25Clinical Significance of Antibiotic Resistance