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

Int J Nanomedicine. 2025 Jun 25:20:8191-8207. doi: 10.2147/IJN.S525411. eCollection 2025.

Abstract

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.

Keywords: cerium oxide nanoparticles; chronic inflammation; nanozymes; oxidative stress; quercetin.

MeSH terms

  • A549 Cells
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / administration & dosage
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Cell Survival / drug effects
  • Cerium* / chemistry
  • Cerium* / pharmacology
  • Cytokines* / metabolism
  • Down-Regulation / drug effects
  • Drug Carriers / chemistry
  • Humans
  • Nanocomposites / chemistry
  • Oxidative Stress / drug effects
  • Porosity
  • Quercetin* / administration & dosage
  • Quercetin* / chemistry
  • Quercetin* / pharmacology
  • Reactive Oxygen Species / metabolism
  • Silicon Dioxide* / chemistry

Substances

  • Cerium
  • Quercetin
  • Silicon Dioxide
  • ceric oxide
  • Cytokines
  • Reactive Oxygen Species
  • Antioxidants
  • Anti-Inflammatory Agents
  • Drug Carriers