Light-drive hydrogen production using titanium-based perovskite is one sustainable way to reduce current reliance on fossil fuels, but its wide applications are still limited by high electron-hole recombination and sluggish surface reaction. Thus, the developments for low-cost and highly efficient co-catalysts remain urgent. Inspired by natural [NiFe]-hydrogenase active center structure, a hydrogenase-mimic, NiCo₂S₄ nanozyme was synthesized, and subsequently decorated onto the CaTiO₃ to catalyze the hydrogen evolution reaction (HER). Among the following test, CaTiO₃ with a 15% loading of NiCo₂S₄ nanozyme exhibited the highest HER rate of 307.76 μmol·g^-1·h^-1, which is 60 times higher than that of the CaTiO₃ alone. The results revealed that NiCo₂S₄ not only significantly increased the charge separation efficiency of the photogenerated carriers, but also substantively lowered the HER activation energy. Mechanism studies show that NiCo₂S₄ readily splits H₂O by forming the Ni(OH)-Co intermediate and only Ni in the bimetallic center alters the oxidation state during the HER process in a manner analogous to the [NiFe]-hydrogenase. In contrast to the often-expensive synthetic catalysts that rely on rare elements such as ruthenium or platinum, this study shows a promising way to develop the nature-inspired cocatalysts to enhance the photocatalysts’ HER performance.

Although great progress has been made in improving hydrogen production, highly efficient catalysts, which are able to produce hydrogen in a fast and steady way at ambient temperature and pressure, are still in large demand. Here, we report a [NiCo]-based hydrogenase mimic, NiCo₂O₄ nanozyme, that can catalyze robust hydrogen evolution spontaneously in water without external energy input at room temperature. This hydrogenase nanozyme facilitates water splitting reaction by forming a three-center Ni–OH–Co bond analogous to the [NiFe]-hydrogenase reaction by using aluminum as electron donor, and realizes hydrogen evolution with a high production rate of 915 L·h⁻¹ per gram of nanozymes, which is hundreds of times higher than most of the natural hydrogenase or hydrogenase mimics. Furthermore, the NiCo₂O₄ nanozyme can robustly disrupt the adhesive oxidized layer of aluminum and enable the full consumption of electrons from aluminum. In contrast to the often-expensive synthetic catalysts that rely on rare elements and consume high energy, we envision that this NiCo₂O₄ nanozyme can potentially provide an upgrade for current hydrogen evolution, accelerate the development of scale-up hydrogen production, and generate a clean energy future.

In the past decade, nanozymes - a unique class of nanomaterials with inherent enzyme-mimetic properties - have fascinated researchers, revealing unexpected enzyme-like activity of nanomaterials previously considered biologically inert. In particular, as metal-free catalyst for biological processes, carbon-based nanozymes have grown in popularity due to their exceptional physical and chemical characteristics. So far, a variety of carbon-based nanozymes with various structures such as fullerene, graphene oxide, carbon dot, carbon nanotube, and carbon nanosphere have been reported possessing a wide range of enzyme-like properties. However, the structure-activity relationship of the carbon-based nanozymes have not yet been comprehensively discussed. In this review, we thoroughly examine the recent findings on the structure-activity connection of carbon nanozymes, in an effort to comprehend the underlying mechanism of carbon nanozymes and throw light on the future direction of the systematic design and construction of functionally specific carbon nanozymes. We also will address the broad range of applications of carbon nanozymes from in vitro detection to replacing specific enzymes in living systems.

During criminal case investigations, blood evidence tracing is critical for criminal investigation. However, the blood stains are often cleaned or covered up after the crime, resulting in trace residue and difficult tracking. Therefore, a highly sensitive and specific method for the rapid detection of human blood stains remains urgent. To solve this problem, we established a nanozyme-based strip for rapid detection of blood evidence with high sensitivity and specificity. To construct reliable nanozyme strips, we synthesized CoFe₂O₄ nanozymes with high peroxidase-like activity by scaling up to gram level, which can be supplied for six million tests, and conjugated antibody as a detection probe in nanozyme strip. The developed CoFe₂O₄ nanozyme strip can detect human hemoglobin (HGB) at a concentration as low as 1 ng/mL, which is 100 times lower than the commercially available colloidal gold strips (100 ng/mL). Moreover, this CoFe₂O₄ nanozyme strip showed high generality on 12 substrates and high specificity to human HGB among 13 animal blood samples. Finally, we applied the developed CoFe₂O₄ nanozyme strip to successfully detect blood stains in three real cases, where the current commercial colloidal gold strip failed to do. The results suggest that the CoFe₂O₄ nanozyme strip can be used as an effective on-scene detection method for human blood stains, and can further be used as a long-term preserved material evidence for traceability inquiry.

Rational design of metallic active sites and its microenvironment is critical for constructing superoxide dismutase (SOD) nanozymes. Here, we reported a novel SOD nanozyme design, with employing graphene oxide (GO) as the framework, and δ-MnO₂ as the active sites, to mimic the natural Mn-SOD. This MnO₂@GO nanozyme exhibited multiscale laminated structures with honeycomb-like morphology, providing highly specific surface area for ·O₂⁻ adsorption and confined spaces for subsequent catalytic reactions. Thus, the nanozyme achieved superlative SOD-like catalytic performance with inhibition rate of 95.5%, which is 222.6% and 1605.4% amplification over GO and MnO₂ nanoparticles, respectively. Additionally, such unique hierarchical structural design endows MnO₂@GO with catalytic specificity, which was not present in the individual component (GO or MnO₂). This multiscale structural design provides new strategies for developing highly active and specific SOD nanozymes.

Single-atom nanozyme (SAzyme) is the hot topic of the current nanozyme research. Its intrinsic properties, such as high activity, stability, and low cost, present great substitutes to natural enzymes. Moreover, its fundamental characteristics, i.e., maximized atom utilizations and well-defined geometric and electronic structures, lead to higher catalytic activities and specificity than traditional nanozymes. SAzymes have been applied in many biomedical areas, such as anti-tumor therapy, biosensing, antibiosis, and anti-oxidation therapy. Here, we will discuss a series of representative examples of SAzymes categorized by their biomedical applications in this review. In the end, we will address the future opportunities and challenges SAzymes facing in their designs and applications.

Nanozymes are nanomaterials with enzyme-like properties that have attracted significant interest owing to their capability to address the limitations of traditional enzymes such as fragility, high cost, and impossible mass production. Over the past decade, a broad variety of nanomaterials have been found to mimic the enzyme-like activity by engineering the active centers of natural enzymes or developing multivalent elements within nanostructures. Carbon nanomaterials with well-defined electronic and geometric structures have served as favorable surrogates of traditional enzymes by mimicking the highly evolved catalytic center of natural enzymes. In particular, by combining the unique electronic, optical, thermal, and mechanical properties, carbon nanomaterials-based nanozymes can offer a variety of multifunctional platforms for biomedical applications. In this review, we will introduce the enzymatic characteristics and recent advances of carbon nanozymes, and summarize their significant applications in biomedicine.