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 (CeO(2)NZs) into mesoporous silica (mSiO(2)) 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.