Mesoporous Silica-Encapsulated Cerium Oxide Nanozymes and Quercetin for Synergistic ROS-Modulated Downregulation of Inflammatory Cytokines

Introduction Combining natural antioxidants with nanozymes represents a promising strategy to enhance therapeutic outcomes in oxidative stress-related diseases. This study integrates quercetin (Que), a plant-derived flavonoid with strong antioxidant activity, and cerium oxide nanozymes (CeO2NZs) into mesoporous silica (mSiO2) to enhance therapeutic efficacy and overcome the poor solubility and bioavailability of natural antioxidants.Methods Large-pore mSiO₂ (11 nm) were synthesized via a sol–gel method to encapsulate cerium oxide nanozymes (CeO₂NZs). Que was loaded using solvent impregnation to obtain (CeO₂/Que)@mSiO₂ nanocomposites. Structural and chemical characterization was performed, and biological evaluations were conducted in A549 cells.Results The incorporation of a large mesopore mSiO₂ (11 nm) significantly enhanced Que loading capacity and its sustained release in cell culture media. The (CeO₂/Que)@mSiO₂ nanocomposite demonstrated excellent biocompatibility, effective ROS scavenging, and significant downregulation of inflammatory cytokines (IL-1β, IL-6, TNF-α) compared to free Que.Conclusion The (CeO₂/Que)@mSiO₂ nanoplatform offers synergistic antioxidant and anti-inflammatory effects, supporting its potential for treating oxidative stress-related inflammatory conditions.