Engineering a multifunctional nanoplatform with cascade catalytic and bidirectional immunomodulatory capacities for integrating sepsis therapy.

INTRODUCTION

Sepsis is a life-threatening condition characterized by organ dysfunction due to a dysregulated immune response to infection. Despite extensive research into its complex pathogenesis, effective clinical treatments remain limited, necessitating novel therapeutic strategies.

OBJECTIVES

This study aims to develop a multifunctional nanozyme-based therapy for severe sepsis, combining broad-spectrum antimicrobial activity and reactive oxygen species (ROS) scavenging to counteract organ injury, immune dysregulation, and high mortality.

METHODS

We designed biocompatible resveratrol-Ag + -Prussian blue nanozymes (ARPB NZs) and evaluated their therapeutic effects in two murine sepsis models: E. coli-induced abdominal infection and cecal ligation puncture (CLP). Mechanistic studies focused on oxidative stress attenuation, cytokine storm suppression, lymphocyte function, and dendritic cell pyroptosis via the NLRP3/caspase-1/GSDMD pathway.

RESULTS

ARPB NZs effectively alleviated organ damage, maintained immune homeostasis by reducing inflammation and oxidative stress, and significantly improved survival rates in both sepsis models. They also inhibited lymphocyte apoptosis and dampened dendritic cell pyroptosis.

CONCLUSION

ARPB NZs represent a promising synergistic strategy for severe sepsis by simultaneously targeting infection and immune dysregulation. This approach may translate into broader applications for infectious diseases.