Ce ₁₂ V ₆ Clusters with Multi‐Enzymatic Activities for Sepsis Treatment

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 Ce₁₂V₆ clusters with a size of 2.19 nm are constructed. The Ce₁₂V₆ clusters show excellent glutathione peroxidase (GPx) -like activity with a significantly lower Michaelis-Menten constant (K_m, 0.0125 mM versus 0.03 mM of natural counterpart) and good activities mimic superoxide dismutase (SOD) and peroxidase (POD). The Ce₁₂V₆ clusters exhibit the ability to scavenge the ROS including O₂ ^·- and H₂O₂ via the cascade reactions of multi-enzymatic activities. Further, the Ce₁₂V₆ clusters 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 Ce₁₂V₆ clusters show promise in the treatment of sepsis.