CeVClusters with Multi-Enzymatic Activities for Sepsis Treatment.

Abstract

Artificial enzymes, especially nanozymes, have attracted wide attention due to their controlled catalytic activity, selectivity, and stability. The rising Cerium-based nanozymes exhibit unique SOD-like activity, and Vanadium-based nanozymes always hold excellent GPx-like activity. However, most inflammatory diseases involve polymerase biocatalytic processes that require multi-enzyme activities. The nanocomposite can fulfill multi-enzymatic activity simultaneously, but large nanoparticles (>10 nm) cannot be excreted rapidly, leading to biosafety challenges. Herein, atomically precise CeVclusters with a size of 2.19 nm are constructed. The CeVclusters show excellent glutathione peroxidase (GPx) -like activity with a significantly lower Michaelis-Menten constant (K, 0.0125 mM versus 0.03 mM of natural counterpart) and good activities mimic superoxide dismutase (SOD) and peroxidase (POD). The CeVclusters exhibit the ability to scavenge the ROS including Oand HOvia the cascade reactions of multi-enzymatic activities. Further, the CeVclusters modulate the proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and consequently rescue the multi-organ failure in the lipopolysaccharide (LPS)-induced sepsis mouse model. With excellent biocompatibility, the CeVclusters show promise in the treatment of sepsis.