Redox Trimetallic Nanozyme with Neutral Environment Preference for Brain Injury

Metal nanozyme has attracted wide interest for biomedicine, and a highly catalytic material in the physiological environment is highly desired. However, catalytic selectivity of nanozyme is still highly challenging, limiting its wide application. Here, we show a trimetallic (triM) nanozyme with highly catalytic activity and environmental selectivity. Enzyme-mimicked investigations find that the triM system possesses multi-enzyme-mimetic activity for removing reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as ¹O₂, H₂O₂, ^•OH, and ^•NO. Importantly, triM nanozyme exhibits the significant neutral environment preference for removing the ^•OH, ¹O₂, and ^•NO free radical, indicating its highly catalytic selectivity. The density functional theory (DFT) calculations reveal that triM nanozyme can capture electrons very easily and provides more attraction to reactive oxygen and nitrogen species (RONS) radicals in the neutral environment. In vitro experiments show that triM nanozyme can improve the viability of injured neural cell. In the LPS-induced brain injury model, the superoxide dismutase (SOD) activity and lipid peroxidation can be greatly recovered after triM nanozyme treatment. Moreover, the triM nanozyme treatment can significantly improve the survival rate, neuroinflammation, and reference memory of injured mice. Present work provides a feasible route for improving selectivity of nanozyme in the physiological environment as well as exploring potential applications in brain science.