Structure,Catalytic Property Of Atom Level Mn₁₂ Cluster And Application In Inflammatory Bowel Disease

Inflammatory Bowel Disease（IBD）is a type of chronic intestinal inflammation that is difficult to cure and recurs,and it can cause the oxidative burst of inflammatory cells,produce a variety of free radicals,and further aggravate the progression of IBD.Studies have shown that nanoparticles（NPs）with catalytic activity and enzyme-like activity can be used to treat IBD by scavenging free radicals,but there are still many defects.For example,most NPs have poor catalytic selectivity,and NPs larger than5.5 nm are difficult to be excreted through the kidney.In response to the above shortcomings,our research group has developed atom level Mn₁₂cluster that naturally targets the colon,and its structure was optimized by doping Ag atoms,aiming to further improve the enzymatic activity and catalytic activity,and be applied in the treatment of IBD and gut microbiota regulation.The specific research content are as follows:（1）The Mn₁₂clusters were synthesized by crystallization method with good water solubility and electrocatalytic activity.By regulating the catalytic properties of Mn₁₂clusters,Ag doped Mn₁₂clusters were further designed and synthesized.Firstly,the structure of the cluster was analyzed by various characterization methods,and the results showed that the precise structure of the clusters were Mn₁₁Ag₁.Secondly,chemical methods were used to test the catalytic activity of the clusters.The results show that the electrochemical oxygen evolution reaction（OER）activity,catalase-like（CAT）activity,and peroxidase-like（POD）activity of Mn₁₁Ag₁clusters are respectively higher than those of pure Mn₁₂clusters 5.3,4.3,and 5.3 times.Moreover,its hydroxyl radical（·OH）scavenging ability was 1.45 times higher than that of pure Mn₁₂clusters.In addition,they also showed equally efficient Glutathione peroxidase（GP_X）-like activity,Superoxide dismutase（SOD）-like activity,and total antioxidant capacity.These results indicate that Mn₁₁Ag₁clusters have high catalytic activity and free radical scavenging ability in vitro.（2）Evaluate the therapeutic effect of tail vein injection of Mn₁₁Ag₁clusters on IBD by establishing an IBD mouse model.By testing the corresponding clinical indicators,we found that Mn₁₁Ag₁clusters can restore colon damage,reduce the level of pro-inflammatory factors,and regulate the balance of oxidative stress markers.The above shows that Mn₁₁Ag₁clusters mediated efficient free radical scavenging ability can not only restore colon injury,but also inhibit the progression of inflammation and oxidative stress injury.（3）To further study the mechanism of Mn₁₁Ag₁clusters in the treatment of IBD.First,it was found that Mn₁₁Ag₁clusters can target the colon of normal mice and colitis mice by implementing intestinal targeting experiments.Secondly,by evaluating the regulatory effect of Mn₁₁Ag₁clusters on IBD-induced gut microbiota disorder,it was found that Mn₁₁Ag₁clusters can maintain the diversity and richness of the gut microbiota,as well as increase short-chain fatty acid producing bacteria and exert anti-inflammatory effects.The above shows that the Mn₁₁Ag₁clusters can not only target the colon naturally,but also regulate the gut microbiota.