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

Nanozymes are nanomaterial-based artificial enzymes. By effectively mimicking catalytic sites of natural enzymes or harboring multivalent elements for reactions, nanozyme systems have successfully served as direct surrogates of traditional enzymes for catalysis. With the rapid development and ever-deepening understanding of nanotechnology, nanozymes offer higher catalytic stability, ease of modification and lower manufacturing cost than protein enzymes. Additionally, nanozymes possess inherent nanomaterial properties, providing not only a simple substitute of enzymes but also a multimodal platform interfacing complex biologic environments. Recent extensive research has focused on designing various nanozyme systems that are responsive to one or multiple substrates by tailored means. Catalytic activities of nanozymes can be regulated by pH, H2O2 and glutathione concentrations and levels of oxygenation in different microenvironments. Moreover, nanozymes can be remotely-controlled via different stimuli, including a magnetic field, light, ultrasound, and heat. Collectively, these factors can be adjusted to maximize the diagnostic and therapeutic efficacies of different diseases in biomedical settings. Therefore, by integrating the catalytic property and inherent nanomaterial nature of nanozyme systems, we anticipate that stimuli-responsive nanozymes will open up new horizons for diagnosis, treatment, and theranostics.

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Nanozyme: new horizons for responsive biomedical applications.

Nanozymes are nanomaterials with intrinsic enzyme-like characteristics that have been booming over the past decade because of their capability to address the limitations of natural enzymes such as low stability, high cost, and difficult storage. Along with the rapid development and ever-deepening understanding of nanoscience and nanotechnology, nanozymes hold promise to serve as direct surrogates of traditional enzymes by mimicking and further engineering the active centers of natural enzymes. In 2007, we reported the first evidence that Fe3O4 nanoparticles (NPs) have intrinsic peroxidase-mimicking activity, and since that time, hundreds of nanomaterials have been found to mimic the catalytic activity of peroxidase, oxidase, catalase, haloperoxidase, glutathione peroxidase, uricase, methane monooxygenase, hydrolase, and superoxide dismutase. Uniquely, a broad variety of nanomaterials have been reported to simultaneously exhibit dual- or multienzyme mimetic activity. For example, Fe3O4 NPs show pH-dependent peroxidase-like and catalase-like activities; Prussian blue NPs simultaneously possess peroxidase-, catalase-, and superoxide dismutase-like activity; and Mn3O4 NPs mimic all three cellular antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Taking advantage of the physiochemical properties of nanomaterials, nanozymes have shown a broad range of applications from in vitro detection to replacing specific enzymes in living systems. With the emergence of the new concept of "nanozymology", nanozymes have now become an emerging new field connecting nanotechnology and biology. Since the landmark paper on nanozymes was published in 2007, we have extensively explored their catalytic mechanism, established the corresponding standards to quantitatively determine their catalytic activities, and opened up a broad range of applications from biological detection and environmental monitoring to disease diagnosis and biomedicine development. Here we mainly focus on our progress in the systematic design and construction of functionally specific nanozymes, the standardization of nanozyme research, and the exploration of their applications for replacing natural enzymes in living systems. We also show that, by combining the unique physicochemical properties and enzyme-like catalytic activities, nanozymes can offer a variety of multifunctional platforms with a broad of applications from in vitro detection to in vivo monitoring and therapy. For instance, targeting antibody-conjugated ferromagnetic nanozymes simultaneously provide three functions: target capture, magnetic separation, and nanozyme color development for target detection. We finally will address the prospect of nanozyme research to become "nanozymology". We expect that nanozymes with unique physicochemical properties and intrinsic enzyme-mimicking catalytic properties will attract broad interest in both fundamental research and practical applications and offer new opportunities for traditional enzymology.

Nanozymes: From New Concepts, Mechanisms, and Standards to Applications.

In the past few decades, researchers have developed lots of artificial enzymes with various materials to mimic the structures and functions of natural enzymes. Recently, nanozymes, nanomaterials with enzyme-like characteristics, are emerging as novel artificial enzymes, and attracting researchers’ enormous interest. Remarkable advances have been made in the area of nanozymes due to their unique properties compared with natural enzymes and classic artificial enzymes. Until now, lots of nanomaterials have been studied to mimic various natural enzymes for wide applications. To highlight the recent progress of nanozymes (especially in bionanotechnology), here we discuss the diverse applications of nanozymes, which range from sensing, imaging, and therapeutics, to logic gates, pollutant removal, water treatment, etc. Finally, we address the current challenges facing nanozyme research as well as possible directions to fulfill their great potential in future.

Nanozymes in bionanotechnology: from sensing to therapeutics and beyond

As a new generation of artificial enzymes, nanozymes have the advantages of high catalytic activity, good stability, low cost, and other unique properties of nanomaterials. Due to their wide range of potential applications, they have become an emerging field bridging nanotechnology and biology, attracting researchers in various fields to design and synthesize highly catalytically active nanozymes. However, the thorough understanding of experimental phenomena and the mechanisms beneath practical applications of nanozymes limits their rapid development. Herein, the progress of experimental and computational research of nanozymes on two issues over the past decade is briefly reviewed: (1) experimental development of new nanozymes mimicking different types of enzymes. This covers their structures and applications ranging from biosensing and bioimaging to therapeutics and environmental protection. (2) The catalytic mechanism proposed by experimental and theoretical study. The challenges and future directions of computational research in this field are also discussed.

Recent Advances in Nanozyme Research

Mechanism of pH-switchable peroxidase and catalase-like activities of gold, silver, platinum and palladium

Construction of C–N bonds from small-molecule precursors through heterogeneous electrocatalysis

Electrochemical formation of C–S bonds from CO2 and small-molecule sulfur species

The development of electrochemical technologies is becoming increasingly important due to their growing part in renewable energy conversion and storage. Within this context, metal organic frameworks (MOFs) are finding an important role as electrocatalysts. Specifically, their molecularly defined structure across several lengths scales endows them functionality not accessible with conventional heterogeneous catalysts. To this end, this perspective will focus on the unique features within MOFs and their analogs that enable them to carry out electrocatalytic reactions in unique ways to synthesize fuels and value-added chemicals from abundant building blocks like CO2 and N2. We start with a brief overview of the initial advent of MOF electrocatalysts prior to moving to overview the forefront of the field of MOF-based electrosynthesis. The main discussion focuses on three principal directions in MOF-based electrosynthesis: multifunctional active sites, electronic modulation, and catalytic microenvironments. To conclude, we identify several challenges in the next stage of MOF electrocatalyst development and offer several key directions to take as the field matures.

Emerging opportunities with metal-organic framework electrosynthetic platforms

The electrochemical conversion of NO3− to NH3 is an emerging route to an essential chemical feedstock and potential fuel. Underpinning the field’s development is the discovery of efficient electrocatalysts and insights into the reaction mechanism. To this end, a Cu-based oxyfluoride, Cu3Al2OF10, prepared through a facile co-precipitation and annealing of the corresponding hydrated fluoride r-Cu3Al2F12(H2O)12, was found to be exceptionally active, attaining a NH3 Faradaic efficiency (FE) of up to 57% for the 8-electron NO3− to NH3 pathway (−0.4 VRHE) with a mass activity of up to 1220 A.g−1 at −0.6 VRHE. Electroanalytical and operando spectroscopic investigations revealed a reversible transition to a phase entailing Cu nanoparticles embedded within the amorphous oxyfluoride matrix that was predominantly responsible for the catalyst’s activity. Overall, this work stands to open avenues for transition metal fluoride materials within the field of N-based electrocatalysis. 

Junnan Li

Papers

Mechanism of pH-switchable peroxidase and catalase-like activities of gold, silver, platinum and palladium

Construction of C–N bonds from small-molecule precursors through heterogeneous electrocatalysis

Electrochemical formation of C–S bonds from CO2 and small-molecule sulfur species

Emerging opportunities with metal-organic framework electrosynthetic platforms

Reversible transition of an amorphous Cu-Al oxyfluoride into a highly active electrocatalyst for NO3− reduction to NH3