Antioxidative Aortic Aneurysm Therapy by a Mn–N4 Biomimetic Site-Engineered Nanocatalyst

Oxidative stress is a major factor in the formation of lethal aortic aneurysm. Traditional molecular antioxidants can only act as reactants to scavenge reactive oxygen species (ROS) through stoichiometric reactions, which are consumed in the process, leading to unsustainable antioxidant effects. This study proposes a nanocatalytic antioxidation strategy for treating aortic aneurysm by constructing an antioxidative biomimetic nanocatalyst, which features a Mn-N₄ tetra-coordinated structure similar to natural heme catalase, providing a sustained catalytic antioxidation effect that can disproportionate H₂O₂ into H₂O and O₂. The underlying structure-function relationship and catalytic pathway of the nanocatalyst are explored, revealing a Mn^III/Mn^V transition mechanism with inner-sphere proton-coupled two-electron transfer. Further cellular and animal investigations demonstrate that the highly antioxidatively active nanocatalyst is capable of eliminating aortal oxidative stress and aortitis to large extents, thus protecting vascular smooth muscle cells and synergistically promoting the morphological and functional recovery of aorta. This nanocatalytic antioxidation strategy holds promise for treating multiple cardiovascular diseases.