A pair of metals can be better than one when the goal is to build artificial enzymes from nanoparticles. A review published on 7 January 2026 in the open-access journal Discover Catalysis surveys the latest structural designs, catalytic mechanisms and applications of bimetallic nanozymes, nanomaterials that combine two metallic elements to mimic the catalytic behaviour of natural enzymes. Written by Zhuo Wen, Yilin Zhao, Heyuan Zhao, Yilang Chen, Gang Xiao, Haijia Su and colleagues, the review organises a fast-growing literature around five structural families and argues that the pairing of two metals is the field’s central design lever, while also flagging the biosafety and scalability questions that still stand between laboratory demonstrations and real-world use.
Nanozymes first appeared as a concept in 2004, when researchers reported that gold nanoparticles functionalised with a specific organic ligand could catalyse transphosphorylation reactions. The field gained momentum in 2007 with the report that iron oxide magnetic nanoparticles possess intrinsic peroxidase-like activity. Since then, nanozymes built from a long list of metals and metal oxides have been synthesised, showing biomimetic activities that include peroxidase, catalase, oxidase, superoxide dismutase and phosphatase functions. Compared with natural enzymes, these materials promise greater stability, lower cost and easier chemical modification, which has driven interest in biomedicine, environmental science and analytical chemistry.
The review is candid about why single-metal nanozymes have struggled. Unmodified nanoparticles such as plain iron oxide, cobalt oxide or ceria of five to twenty nanometres bind their target substrate hydrogen peroxide only at millimolar concentrations while reacting with interferents at micromolar levels, giving selectivity five orders of magnitude worse than natural peroxidase. Their turnover numbers sit near one hundred per second, some three to four orders of magnitude below natural enzymes. In saline or serum they aggregate within hours and lose more than half their activity, and in whole blood they oxidise and dissolve within minutes, with an intracellular half-life under six hours. Bimetallic designs, the authors argue, attack these weaknesses through the synergistic interaction of two metals’ catalytic properties.
Structurally, the review divides bimetallic nanozymes into five categories: core-shell structures, nanoclusters, carbon nanostructures, metal-organic frameworks and hybrid nanoflowers. In core-shell particles, one metal forms a defined core around which a second metal shell grows, and the electronic interaction between the two modulates catalytic performance while the shell protects the core from oxidation or corrosion. One cited example is a gold-platinum core-shell nanoparticle synthesised through a DNA-encoded method, in which the DNA sequence influenced where platinum deposited on the gold core, creating more active sites on high-energy surfaces. A related spherical gold-platinum particle made by chemical reduction showed oxidase-like activity that glutathione could inhibit through its thiol groups, enabling glutathione detection with a limit as low as 34 nanomolar and a linear response between 0.1 and 1.0 micromolar.
The review also highlights a copper-silver alloy nanozyme loaded with the prodrug AQ4N, built by a two-step seed-mediated growth method with a specific surface area of 300.6 square metres per gram and pores of roughly 3.8 nanometres. Under the weakly acidic conditions of the tumour microenvironment, and in the presence of ferrous cytochrome c, the particles depleted intracellular oxygen by 46 percent and generated reactive oxygen species. Density functional theory calculations indicated a stronger interaction between the copper-silver alloy and cytochrome c than with pure metals, with electron transfer across the alloy-protein interface enhancing catalytic activity. The authors caution, however, that synthesising such core-shell structures remains complex, and that some systems can lose activity through surface oxidation or component loss during storage.
Nanoclusters, sized between one and ten nanometres, exploit quantum effects and precise atomic composition. One study doped a single silver atom into a 25-atom gold cluster protected by mercaptopropionic acid ligands, and this single-atom substitution altered the cluster’s electronic structure and significantly enhanced its peroxidase-like activity. Another team mixed gold and silver into fluorescent nanoclusters averaging 1.78 nanometres in diameter with a quantum yield of 33.18 percent, whose fluorescence remained stable across salt concentrations and a pH range of 6.0 to 11.0. On the carbon-based side, a composite of gold nanoparticles, cerium dioxide and graphene oxide showed strong selectivity for nitrite detection, with recoveries above 60 percent and relative standard deviations of 0.4 to 1.7 percent in tap water testing, though the review notes that multi-step synthesis risks metal aggregation and that carbon layers can partially shield active sites.
Metal-organic frameworks, porous crystalline materials built from metal nodes and organic linkers, raise active-site density and create charge-transfer channels. A copper-cobalt framework electrode demonstrated a sensitivity of 8304.4 milliamperes per millimolar per square centimetre with a detection limit of 0.023 millimolar and strong resistance to common interferents such as ascorbic acid, uric acid and dopamine. Framework nanozymes also appear in environmental work: a manganese-cobalt oxide nanofibre membrane derived from a bimetallic framework was developed for colorimetric phenol detection, and a europium-cerium framework nanozyme achieved 87.6 percent degradation of the pesticide paraoxon within 180 minutes, compared with 55.3 percent for the undoped framework, alongside a fluorescent detection limit of 5.5 nanomolar. Hybrid nanoflowers, the fifth family, offer large surface areas through petal-like architectures; silver-copper-phosphate variants detected thiol-containing molecules at limits of 800 picomolar for thiophenol and 60 picomolar for thiocholine, and an aptamer-functionalised flower reached a mercury adsorption capacity of 1073.19 milligrams per gram.
On the application side, the review catalogues clinical colorimetric sensing, therapy and environmental monitoring. A core-shell copper-manganese oxide nanozyme enabled uric acid detection with limits of 0.036 micromolar in buffer and 0.16 micromolar in human serum, and in a small set of 20 clinical blood samples it achieved an area under the receiver operating characteristic curve of 0.940, with a 95 percent confidence interval of 0.737 to 0.997. A palladium-iridium core-shell probe for gastric cancer biomarkers reached a detection limit of 10 picograms per millilitre, 200 times lower than without signal amplification, correctly classifying eight positive and 28 negative samples among 36 clinical sera within 25 minutes. In antibacterial work, a copper-cobalt sulfide nanozyme combined with hydrogen peroxide accelerated MRSA-infected wound closure to 83.7 percent after six days, versus 59.0 percent in controls, and a cobalt-iron nanodot formulation killed more than 95 percent of methicillin-resistant bacteria within five minutes, with a haemolysis rate below one percent at high concentrations. In oncology studies, a copper-iron-phosphide nanozyme with 66.9 percent photothermal conversion raised tumour inhibition from 83.7 percent to 99.8 percent under near-infrared light in mouse models, and a gold-ruthenium cluster nanozyme was engineered to reduce doxorubicin-induced heart injury without compromising antitumour efficacy. Environmental platforms include a platinum-nickel photoelectrochemical aptasensor for the antibiotic sulfamethoxazole with a detection limit of 37.2 femtograms per millilitre, and a cobalt-iron Prussian blue analogue sensor for glyphosate reaching 0.12 nanomolar by surface-enhanced Raman spectroscopy, with spike recoveries between 97.64 and 104.95 percent.
The review closes with a sober assessment of what remains unresolved. Bimetallic nanozymes still face synthesis that relies largely on empirical trial and error, catalytic efficiency that trails natural enzymes because the underlying mechanisms remain incompletely understood, and open questions about biological safety, toxicity, stability, reproducibility and the absence of standardised protocols. The authors propose artificial-intelligence-guided density functional theory platforms for atomically precise design, in situ characterisation methods to decode synergistic mechanisms, surface engineering such as PEGylation and biodegradable coatings to mitigate risk, and cross-disciplinary certification to accelerate translation. As a review, the article synthesises and evaluates published studies rather than presenting new experimental results, and many of the cited performances come from cell, animal or sensor studies that have not yet been validated in clinical practice. Even so, the through-line is clear: pairing two metals, and engineering the structures that host them, has become the defining strategy for turning enzyme-mimicking nanomaterials from laboratory curiosities into practical sensing, therapeutic and environmental tools.
Subject of Research: Bimetallic nanozymes: structural design, catalytic mechanisms and applications
Article Title: Engineering bimetallic nanozyme structures for enhanced catalytic activity and multifunctional applications
Article References: Wen, Z., Zhao, Y., Zhao, H., Chen, Y., Xiao, G., & Su, H. (2026). Engineering bimetallic nanozyme structures for enhanced catalytic activity and multifunctional applications. Discover Catalysis, 3(1), Article 2. https://doi.org/10.1007/s44344-025-00030-7
Image Credits: AI Generated
DOI: 10.1007/s44344-025-00030-7
Keywords: bimetallic nanozymes, nanotechnology, enzyme mimicry, core-shell nanoparticles, metal-organic frameworks, biosensors, catalysis, antibacterial therapy, cancer treatment, environmental monitoring, nanoclusters, hybrid nanoflowers
News Source: Bethany Barker. (October 30, 2026). Bimetallic Nanozymes Pair Two Metals to Push Enzyme-Mimicking Catalysis Further. Scienmag.
