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 Ce ₁₂ V ₆ clusters with a size of 2.19 nm are constructed. The Ce ₁₂ V ₆ 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 Ce ₁₂ V ₆ clusters exhibit the ability to scavenge the ROS including O ₂ ^·- and H ₂ O ₂ via the cascade reactions of multi-enzymatic activities. Further, the Ce ₁₂ V ₆ 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 Ce ₁₂ V ₆ clusters show promise in the treatment of sepsis.
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