Over the past few decades, researchers have established artificial enzymes as highly stable and low-cost alternatives to natural enzymes in a wide range of applications. A variety of materials including cyclodextrins, metal complexes, porphyrins, polymers, dendrimers and biomolecules have been extensively explored to mimic the structures and functions of naturally occurring enzymes. Recently, some nanomaterials have been found to exhibit unexpected enzyme-like activities, and great advances have been made in this area due to the tremendous progress in nano-research and the unique characteristics of nanomaterials. To highlight the progress in the field of nanomaterial-based artificial enzymes (nanozymes), this review discusses various nanomaterials that have been explored to mimic different kinds of enzymes. We cover their kinetics, mechanisms and applications in numerous fields, from biosensing and immunoassays, to stem cell growth and pollutant removal. We also summarize several approaches to tune the activities of nanozymes. Finally, we make comparisons between nanozymes and other catalytic materials (other artificial enzymes, natural enzymes, organic catalysts and nanomaterial-based catalysts) and address the current challenges and future directions (302 references).

Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes

Because of the high catalytic activities and substrate specificity, natural enzymes have been widely used in industrial, medical, and biological fields, etc. Although promising, they often suffer from intrinsic shortcomings such as high cost, low operational stability, and difficulties of recycling. To overcome these shortcomings, researchers have been devoted to the exploration of artificial enzyme mimics for a long time. Since the discovery of ferromagnetic nanoparticles with intrinsic horseradish peroxidase-like activity in 2007, a large amount of studies on nanozymes have been constantly emerging in the next decade. Nanozymes are one kind of nanomaterials with enzymatic catalytic properties. Compared with natural enzymes, nanozymes have the advantages such as low cost, high stability and durability, which have been widely used in industrial, medical, and biological fields. A thorough understanding of the possible catalytic mechanisms will contribute to the development of novel and high-efficient nanozymes, and the rational regulations of the activities of nanozymes are of great significance. In this review, we systematically introduce the classification, catalytic mechanism, activity regulation as well as recent research progress of nanozymes in the field of biosensing, environmental protection, and disease treatments, etc. in the past years. We also propose the current challenges of nanozymes as well as their future research focus. We anticipate this review may be of significance for the field to understand the properties of nanozymes and the development of novel nanomaterials with enzyme mimicking activities.

Nanozymes: Classification, Catalytic Mechanisms, Activity Regulation, and Applications

Gold nanoparticles (AuNPs) with simultaneous plasmonic and biocatalytic properties provide a promising approach to developing versatile bioassays However, the combination of AuNPs’ intrinsic enzyme-mimicking properties with their surface-enhanced Raman scattering (SERS) activities has yet to be explored Here we designed a peroxidase-mimicking nanozyme by in situ growing AuNPs into a highly porous and thermally stable metal–organic framework called MIL-101 The obtained AuNPs@MIL-101 nanozymes acted as peroxidase mimics to oxidize Raman-inactive reporter leucomalachite green into the active malachite green (MG) with hydrogen peroxide and simultaneously as the SERS substrates to enhance the Raman signals of the as-produced MG We then assembled glucose oxidase (GOx) and lactate oxidase (LOx) onto AuNPs@MIL-101 to form AuNPs@MIL-101@GOx and AuNPs@MIL-101@LOx integrative nanozymes for in vitro detection of glucose and lactate via SERS Moreover, the integrative nanozymes were further explored for monitoring

Surface-Enhanced Raman Scattering Active Gold Nanoparticles with Enzyme-Mimicking Activities for Measuring Glucose and Lactate in Living Tissues

Nanoparticles and proteins are similar in a number of aspects, and using nanoparticles to mimic the catalytic function of enzymes is an interesting yet challenging task. Impressive developments have been made over the past two decades on this front. The term nanozyme was coined to refer to nanoparticlebased enzyme mimics. To date, many different types of nanozymes have been reported to catalyze a broad range of reactions for chemical, analytical, and biomedical applications. Since chemical reactions happen mainly on the surface of nanozymes, an interesting aspect for investigation is surface modification. In this review, we summarize three types of nanozyme materials catalyzing various reactions with a focus on their surface chemistry. For metal oxides, cerium oxide and iron oxide are discussed as they are the most extensively studied. Then, gold nanoparticles and graphene oxide are reviewed to represent metallic and carbon nanomaterials, respectively. Types of modifications include ions, small molecules, and polymers mainly by physisorption, while in a few cases, covalent modifications were also employed. The functional aspect of such modification is to improve catalytic activity, substrate specificity, and stability. Future perspectives of this field are speculated at the end of this review.

Surface modification of nanozymes

Creating artificial enzymes that mimic the complexity and function of natural systems has been a great challenge for the past two decades. In this Progress Report, the focus is on recently discovered "hidden talents" of gold nanomaterials in artificial enzymes, including mimicking of nuclease, esterase, silicatein, glucose oxidase, peroxidase, catalase, and superoxide dismutase. These unexpected enzyme-like activities can be ascribed to nano-gold itself or the functional groups present on surrounding monolayer.

Jia Jia Zheng

Papers

Visual observation of the mercury-stimulated peroxidase mimetic activity of gold nanoparticles