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Ce12V6 Clusters with Multi-Enzymatic Activities for Sepsis Treatment
Di Liu1, Si Sun1, Huanhuan Qiao1
1Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China.
Advanced Healthcare Materials
|August 12, 2024
Summary
Atomically precise Ce12V6 clusters (2.19 nm) offer multi-enzyme activity, mimicking glutathione peroxidase (GPx), superoxide dismutase (SOD), and peroxidase (POD). These nanozymes effectively scavenge reactive oxygen species (ROS) and reduce inflammatory cytokines, showing promise for sepsis treatment.
Area of Science:
- Biomimetic chemistry
- Nanotechnology
- Catalysis
Background:
- Nanozymes offer controlled catalytic activity, selectivity, and stability, with cerium-based nanozymes showing SOD-like activity and vanadium-based nanozymes exhibiting GPx-like activity.
- Inflammatory diseases often involve multi-enzyme biocatalytic processes, necessitating agents with combined enzymatic functions.
- Existing nanocomposites with multi-enzymatic activity face biosafety challenges due to large nanoparticle sizes (>10 nm) hindering rapid excretion.
Purpose of the Study:
- To construct atomically precise nanozyme clusters with combined GPx, SOD, and POD activities.
- To evaluate the reactive oxygen species (ROS) scavenging capabilities of the nanozymes.
- To assess the therapeutic potential of the nanozymes in a sepsis mouse model.
Main Methods:
- Synthesis of atomically precise Ce12V6 clusters (2.19 nm).
- In vitro evaluation of GPx, SOD, and POD-like activities, including Michaelis-Menten kinetics.
- Assessment of ROS scavenging via cascade reactions.
- In vivo study using a lipopolysaccharide (LPS)-induced sepsis mouse model to evaluate anti-inflammatory effects and organ protection.
Main Results:
- Ce12V6 clusters demonstrated excellent GPx-like activity (Km = 0.0125 mM) and good SOD and POD mimicry.
- The nanozymes effectively scavenged ROS, including superoxide radicals (O2·−) and hydrogen peroxide (H2O2), through cascade reactions.
- Ce12V6 clusters modulated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and rescued multi-organ failure in the sepsis model.
- The nanozymes exhibited excellent biocompatibility.
Conclusions:
- Atomically precise Ce12V6 clusters provide a size-controlled platform for multi-enzymatic nanozymes.
- These nanozymes effectively neutralize ROS and mitigate inflammation, offering a promising therapeutic strategy for sepsis.
- The small size (<10 nm) of Ce12V6 clusters suggests improved biosafety profiles for potential clinical translation.
