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Superoxide ions are reactive radicals that play critical roles in biological systems, normally regulated by the enzyme superoxide dismutase. While artificial enzyme mimics such as nano ceria exist, their practical application is limited by toxicity, poor specificity, and aggregation. To address this, a bimetallic copper and zinc single-atom nanozyme was synthesised to mimic the natural structure and function of superoxide dismutase. In laboratory testing, the nanozyme effectively captured superoxide radicals and inhibited nitro-blue tetrazolium reduction. It achieved a catalytic activity of 7820 units per milligram, outperforming the natural enzyme, with a half-maximal inhibitory concentration of 0.115 micrograms per millilitre. Unlike other dual-metal nanozymes, it selectively mimics superoxide dismutase without exhibiting oxidase or peroxidase activity. Furthermore, tests using cigarette smoke extract demonstrated its biological safety and practical capability to neutralise oxidative stress.
Excessive reactive oxygen species drive cellular damage across many health conditions. While natural enzymes degrade easily and existing nanomaterial substitutes can be toxic or unselective, this single-atom nanozyme matches the structure of natural enzymes to provide higher catalytic activity without unwanted side reactions, presenting a cleaner method to counter oxidative stress.
The findings suggest applications in treatments for cardiovascular, inflammatory, and neurodegenerative diseases, as well as ingredients for cosmetic anti-ageing and skin protection products. Potential users include pharmaceutical developers and skincare formulation manufacturers. Currently, the technology represents early-stage laboratory research, supported by chemical assays and in vitro testing in cigarette smoke extract, and requires further clinical development before real-world adoption.
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The superoxide ion (O<sup>2•-</sup>), 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<sup>2•-</sup>. Traditionally, nano ceria (CeO<sub>2</sub>) is used for SOD mimicry due to its Ce<sup>3+</sup>/Ce<sup>4+</sup> 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<sub>50</sub>) of 0.115 µg mL<sup>-1</sup> and a catalytic activity of 7820 U mg<sup>-1</sup>, compared to 4264 U mg<sup>-1</sup> 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.
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DOI: 10.1002/smll.202503879
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