Targeted Modulation of Redox and Immune Homeostasis in Acute Lung Injury Using a Thioether-Functionalized Dendrimer

Area of Science:

• Nanomedicine
• Immunology
• Biochemistry

Background:

• Acute lung injury (ALI) precedes acute respiratory distress syndrome, characterized by oxidative stress and inflammation disrupting lung homeostasis.
• Current treatments for ALI face challenges due to complex pathophysiological mechanisms involving redox imbalance and immune dysregulation.

Purpose of the Study:

• To develop and evaluate an internally functionalized thioether-enriched dendrimer, Sr-G4-PEG, for simultaneous scavenging of reactive oxygen species (ROS) and proinflammatory cytokines.
• To investigate the potential of Sr-G4-PEG in restoring redox and immune homeostasis in the context of acute lung injury.

Main Methods:

• Synthesis of Sr-G4-PEG dendrimers utilizing thiol-ene "click" chemistry for thioether moiety incorporation.
• Evaluation of Sr-G4-PEG's capacity to scavenge ROS and sequester proinflammatory cytokines.
• Assessment of Sr-G4-PEG's therapeutic effects on ALI models, including modulation of the NLRP3-pyroptosis pathway and key pathological markers.

Main Results:

• Sr-G4-PEG effectively scavenges ROS and sequesters proinflammatory cytokines, demonstrating synergistic therapeutic effects.
• Treatment with Sr-G4-PEG significantly alleviates ALI symptoms, including reduced alveolar bleeding and inflammatory cell infiltration.
• The dendrimer modulates the NLRP3-pyroptosis pathway, contributing to restored redox and immune homeostasis.

Conclusions:

• Sr-G4-PEG is a promising nanotechnological agent for treating acute lung injury by remodeling redox and immune balance.
• Dendrimer-based nanomedicine holds significant potential for addressing respiratory pathologies like ALI.