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

Abstract

Conspectus 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.

Peroxidase‐Like Nanozymes Induce a Novel Form of Cell Death and Inhibit Tumor Growth In Vivo

“…[ 15,16 ] Along with the rapid development and deepening understanding of nanoscience and nanotechnology, nanozymes hold promise to serve as direct surrogates of traditional enzymes. [ 17–19 ] However, so far, there have been limited descriptions of the biological characteristics of nanozymes in cells or in vivo. We demonstrated in this paper that nanomaterials with peroxidase‐like properties inhibited tumor growth by inducing a novel form of RAS‐activated oxidative cell death.…”

Nanozymes: A New Disease Imaging Strategy

“…(C) Peroxidase nanozymes for the pathological identification of unstable atherosclerotic plaques from patients with symptomatic carotid disease. Reproduced with permission from ref(Liang and Yan, 2019), © 2019, American Chemical Society.…”

Recent Advances in Enzyme-Nanostructure Biocatalysts with Enhanced Activity

“…In this system, the intrinsic glucose oxidase and peroxidase activities of Au nanoparticles provided favorable proton gradient, driving the oxidative phosphorylation of ATP synthase as efficiently as natural mitochondria. In conclusion, nanozymes have been booming in recent years and providing a novel way for designing highly efficient multienzyme systems [60,101,102].…”

“…A great deal of effort has also been made to design nanostructured supports with a variety of components including noble metal (e.g., Au) [23,24], metal oxides (e.g., Cu 2 O, Fe 3 O 4 , SiO 2 , Ti 8 O 15 , alumina) [16,25-33], polymer (e.g., Cu 2+ /PAA/PPEGA matrix, aldehyde-derived Pluronic polymer, polycaprolactone) [34-36], metal-organic frameworks (e.g., zeolitic imidazolate framework) [37-39], carbon based (e.g., carbon dots, carbon nanotubes) [40-44], and complex compounds (e.g., Cu 3 (PO 4 ) 2 ·3H 2 O, Ca 3 (PO 4 ) 2 , Co 3 (PO 4 ) 2 ·8H 2 O, Mn 3 (PO 4 ) 2 , Ca 8 H 2 (PO 4 ) 6 , Cu 4 (OH) 6 )SO 4 , CaHPO 4 , Zn 3 (PO 4 ) 2 , Mg-Al layered double hydroxide, CdSe/ZnS quantum dots) [17,[45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. These representative supports, which possess unique chemical and physical properties, such as controllable release of ion activator and synergic catalysts and response to external stimuli, are able to regulate the enzyme-support interaction and eventually lead to an unprecedented enhancement in immobilized enzyme activity [7,60,61].Overall, recent years have witnessed great success in the interactions between artificial nanostructured supports and natural enzymes for enhanced activity. This review will focus on recent advances in this field in the past 10 years, with an emphasis on various mechanisms behind the boosted catalytic activities, including reduced mass transfer limitation, interfacial ion activation, local heating effect, synergistic effects, conformational changes, substrate channeling and so on.…”