Abstract
Sepsis remains a major challenge in critical care, with high mortality despite ongoing improvements in treatment. The early uncontrolled burst of reactive oxygen and nitrogen species (RONS) and cytokine storms form a vicious cycle, ultimately leading to multiple organ dysfunction syndrome (MODS). The absence of effective therapies to interrupt this process is likely a key reason for poor outcomes. In recent years, the emergence of nanozymes has represented a transformative breakthrough in addressing this challenge. With strong antioxidant capacity, high stability, and low cost, nanozymes surpass conventional antioxidants and offer a promising therapeutic strategy for sepsis, especially through effective redox regulation. Nanozymes not only efficiently scavenge diverse RONS but also inhibit hyperactivated inflammatory pathways, thereby breaking the fatal vicious cycle between oxidative stress and cytokine storms. This provides a novel approach for immunomodulation and organ protection in sepsis. This review summarizes the key role of redox imbalance in sepsis progression and the therapeutic potential of nanozymes targeting redox imbalance, discusses their in vivo metabolic distribution and biosafety, and outlines prospects for future clinical translation and development. The objective is to provide insights that facilitate the development of innovative therapies targeting the RONS-inflammation axis in sepsis.