Cascade Reactions Catalyzed by Gold Hybrid Nanoparticles Generate CO Gas Against Periodontitis in Diabetes

Abstract The treatment of diabetic periodontitis poses a significant challenge due to the presence of local inflammation characterized by excessive glucose concentration, bacterial infection, and high oxidative stress. Herein, mesoporous silica nanoparticles (MSN) are embellished with gold nanoparticles (Au NPs) and loaded with manganese carbonyl to prepare a carbon monoxide (CO) enhanced multienzyme cooperative hybrid nanoplatform (MSN‐Au@CO). The Glucose‐like oxidase activity of Au NPs catalyzes the oxidation of glucose to hydrogen peroxide (H 2 O 2 ) and gluconic acid，and then converts H 2 O 2 to hydroxyl radicals (•OH) by peroxidase‐like activity to destroy bacteria. Moreover, CO production in response to H 2 O 2 , together with Au NPs exhibited a synergistic anti‐inflammatory effect in macrophages challenged by lipopolysaccharides. The underlying mechanism can be the induction of nuclear factor erythroid 2‐related factor 2 to reduce reactive oxygen species, and inhibition of nuclear factor kappa‐B signaling to diminish inflammatory response. Importantly, the antibacterial and anti‐inflammation effects of MSN‐Au@CO are validated in diabetic rats with ligature‐induced periodontitis by showing decreased periodontal bone loss with good biocompatibility. To summarize, MSN‐Au@CO is fabricate to utilize glucose‐activated cascade reaction to eliminate bacteria, and synergize with gas therapy to regulate the immune microenvironment, offering a potential direction for the treatment of diabetic periodontitis.