Mesoporous engineering of metal–phenolic artificial enzymes for enhanced oxidative stress mitigation

Catalytic antioxidant materials are crucial in medical research, yet current research efforts focus mainly on coordination environments while overlooking physical structures, such as porosity and surface area, a limitation that hinders free radical interaction and reduces antioxidant efficacy. Herein, a conceptual framework is proposed for the development of mesoporous metal-polyphenolic artificial enzymes (MPAEs) (mPDA-Cu), effectively addressing these limitations by integrating catalytically activate centers and maximizing the accessible surface area. The pore confinement achieved by intermediate pore engineering inhibits the densification of active centers and enhances the hydrogen atom transfer and electron transfer processes. Notably, mPDA-Cu with a mesoporous structure displays superior catalase-like (CAT-like) activity, efficiently decomposing H₂O₂, which is approximately 3.4-fold higher than that of non-mesoporous aPDA-Cu, and its oxygen generation capacity is enhanced by ∼2.9 times. Owing to its CAT-mimetic activity, mPDA-Cu can effectively decrease intracellular ROS levels and facilitate oxygen production, thereby mitigating hypoxia induced by oxidative stress. This study establishes that engineering mesoporous MPAEs is key for enhancing their catalytic antioxidant properties, which offers a straightforward and efficient platform for the development of high-performance, biocompatible antioxidant nanocatalysts aimed at treating oxidative stress-related pathologies.