Bimetallic Cu/Zn Single‐Atom Nanozyme with Superoxide Dismutase‐Like Activity

Abstract The superoxide ion (O 2•− ), a radical species, is significant in chemical and biological systems. Nanozymes, enzyme‐mimicking nanomaterials, have been developed to replicate superoxide dismutase (SOD), which counters O 2•− . Traditionally, nano ceria (CeO 2 ) is used for SOD mimicry due to its Ce 3+ /Ce 4+ cycling ability, but issues like toxicity, biodistribution, aggregation, and specificity hinder practical use. Single‐atom nanozymes (SANs) offer a solution, with metal centers mimicking natural metal‐based enzymes. A Cu/Zn bimetallic SAN is synthesized, structurally resembling natural SOD and exhibiting comparable activity. Its performance is assessed by capturing superoxide radicals and inhibiting Nitro‐blue tetrazolium (NBT) photoreduction to blue Formazan. The Cu/Zn‐SAN shows a half‐maxima inhibitory concentration (IC 50 ) of 0.115 µg mL −1 and a catalytic activity of 7820 U mg −1 , compared to 4264 U mg −1 for the natural SOD enzyme. Unlike many dual‐metal nanozymes with multiple ROS activities, Cu/Zn‐SAN selectively mimics SOD activity with no detectable oxidase or peroxidase‐like behavior. Additionally, its performance in cigarette smoke extract demonstrates its practical relevance and biological safety. These findings highlight its potential for reducing oxidative stress in cardiovascular, inflammatory, and neurodegenerative diseases, as well as applications in cosmetic anti‐aging products and skin protection, offering a promising alternative to traditional nanozymes.