Au/CeO₂ Nanozyme Scaffold Boosts Electron and Hydrogen Transfer for NIR-Enhanced Chemodynamic Therapy

CeO₂ nanozymes have demonstrated the potential to enhance biological scaffolds with chemodynamic therapy. However, their catalytic efficacy is limited by the slow conversion of Ce⁴⁺ to Ce³⁺ and the lack of substrates like H₂O₂ and H⁺. To address these challenges, we adopted a dual-pronged strategy that utilized the plasmonic resonance of Au nanoparticles and their glucose-oxidase mimicry to boost electron and hydrogen transfer. Specifically, we integrated Au/CeO₂ nanozymes into poly-l-lactic acid scaffolds via selective laser sintering. This conversion of Ce³⁺ to Ce⁴⁺ in the scaffolds enhanced the reduction of H₂O₂ to a hydroxyl radical, inducing oxidative stress in tumor cells. The Au nanoparticles played a crucial role in boosting the Ce³⁺/Ce⁴⁺ catalytic cycle by providing both the energy and the catalytic substrates. They recycled Ce⁴⁺ back to Ce³⁺ by exploiting plasmonic-induced hot electrons and catalyzed glucose oxidation to supply H₂O₂ and H⁺. Our nanoscale and atomic-scale simulations confirmed that the Au/CeO₂ hybrid structure utilized near-field coupling to amplify the plasmonic resonance and the Au-O-Ce bridge reduced the electron transfer barrier. Consequently, the Au/CeO₂ scaffold decreased the activation energy from 22.57 to 9.92 kJ/mol. These findings highlight the significant promise of the Au/CeO₂ nanozyme scaffold for NIR-enhanced chemodynamic therapy.