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.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
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, H
2
O
2
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.
Nanozymes are nanomaterial-based artificial enzymes.
Superoxide dismutases (SODs) are a group of metalloenzymes that catalyze the dismutation of superoxide radicals (O
2
&z.rad;
−
) into hydrogen peroxide (H
2
O
2
) and oxygen (O
2
). As the first line ...of defense against reactive oxygen species (ROS)-mediated damage, SODs are expected to play an important role in the treatment of oxidative stress-related diseases. However, the clinical applications of SODs have been severely limited by their structural instability and high cost. Compared with natural enzymes, nanozymes, nanomaterials with enzyme-like activity, are more stable, and economical, can be easily modified and their activities can be adjusted. Due to their excellent characteristics, nanozymes have attracted widespread attention in recent years and are expected to become effective substitutes for natural enzymes in many application fields. Importantly, some nanozymes with SOD-like activity have been developed and proved to have a mitigating effect on diseases caused by oxidative stress. These studies on SOD-like nanozymes provide a feasible strategy for breaking through the dilemma of SOD clinical applications. However, at present, the specific catalytic mechanism of SOD-like nanozymes is still unclear, and many important issues need to be resolved. Although there are many comprehensive reviews to introduce the overall situation of the nanozyme field, the research on SOD-like nanozymes still lacks a systematic review. From the structure and mechanism of natural SOD enzymes to the structure and regulation of SOD-like nanozymes, and then to the measurement and application of nanozymes, this review systematically summarizes the recent progress in SOD-like nanozymes. The existing shortcomings and possible future research hotspots in the development of SOD-like nanozymes are summarized and prospected. We hope that this review would provide ideas and inspirations for further research on the catalytic mechanism and rational design of SOD-like nanozymes.
This review summarizes catalytic mechanisms, regulatory factors, measurement methods and various applications of SOD-like nanozymes, as well as proposes the current challenges and prospects in the development of SOD-like nanozymes.
Artificial organelles are compartmentalized nanoreactors, in which enzymes or enzyme‐mimic catalysts exhibit cascade catalytic activities to mimic the functions of natural organelles. Importantly, ...research on artificial organelles paves the way for the bottom‐up design of synthetic cells. Due to the separation effect of microcompartments, the catalytic reactions of enzymes are performed without the influence of the surrounding medium. The current techniques for synthesizing artificial organelles rely on the strategies of encapsulating enzymes into vesicle‐structured materials or reconstituting enzymes onto the microcompartment materials. However, there are still some problems including limited functions, unregulated activities, and difficulty in targeting delivery that hamper the applications of artificial organelles. The emergence of nanozymes (nanomaterials with enzyme‐like activities) provides novel ideas for the fabrication of artificial organelles. Compared with natural enzymes, nanozymes are featured with multiple enzymatic activities, higher stability, easier to synthesize, lower cost, and excellent recyclability. Herein, the most recent advances in nanozyme‐based artificial organelles are summarized. Moreover, the benefits of compartmental structures for the applications of nanozymes, as well as the functional requirements of microcompartment materials are also introduced. Finally, the potential applications of nanozyme‐based artificial organelles in biomedicine and the related challenges are discussed.
Nanozymes are promising candidates for the construction of artificial organelles. Compared with natural enzymes, nanozymes exhibit superiorities in high stability, flexibility for synthesis (being synthesized directly in the compartment), and multi‐enzymatic activities (showing different enzymatic activities simultaneously). Based on these advantages, nanozyme‐based artificial organelles present potential applications in antioxidant therapy, tumor treatment, and organelle dysfunction disease treatment.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tumor hypoxia compromises the effects of photodynamic therapy that consumes oxygen in the therapeutic process. Herein, a platinum (Pt)-carbon-integrated nanozyme with favorable catalase-like activity ...and photosensitizing properties was successfully constructed by immobilizing an ultrasmall Pt nanozyme into a MOF-derived carbon nanozyme through an
in situ
reduction strategy. The integration of a Pt nanozyme significantly improves the catalase activity of a carbon nanozyme that can effectively catalyze the decomposition of endogenous hydrogen peroxide to produce oxygen to improve the effects of photodynamic therapy. In addition, the integration of a Pt nanozyme also enhances the intrinsic photothermal performance of a carbon nanozyme. Combining the improved catalase-like activity with the enhanced photothermal properties together, the Pt-carbon nanozyme exhibits remarkable tumor inhibition ability
in vivo
. Thus, utilizing the enzymatic activity and photothermal/photosensitizing properties of nanozymes has great potential to overcome the limitations of traditional therapeutic strategies, and could inspire new directions for nanozyme-based biomedical applications.
Tumor hypoxia compromises the effects of photodynamic therapy that consumes oxygen in the therapeutic process.
Iron oxide nanoparticles have been widely used in many important fields due to their excellent nanoscale physical properties, such as magnetism/superparamagnetism. They are usually assumed to be ...biologically inert in biomedical applications. However, iron oxide nanoparticles were recently found to also possess intrinsic enzyme-like activities, and are now regarded as novel enzyme mimetics. A special term, "Nanozyme", has thus been coined to highlight the intrinsic enzymatic properties of such nanomaterials. Since then, iron oxide nanoparticles have been used as nanozymes to facilitate biomedical applications. In this review, we will introduce the enzymatic features of iron oxide nanozyme (IONzyme), and summarize its novel applications in biomedicine.
Ischemic stroke (IS) is one of the most common causes of disability and death. Thrombolysis and neuroprotection are two current major therapeutic strategies to overcome ischemic and reperfusion ...damage. In this work, a novel peptide‐templated manganese dioxide nanozyme (PNzyme/MnO2) is designed that integrates the thrombolytic activity of functional peptides with the reactive oxygen species scavenging ability of nanozymes. Through self‐assembled polypeptides that contain multiple functional motifs, the novel peptide‐templated nanozyme is able to bind fibrin in the thrombus, cross the blood–brain barrier, and finally accumulate in the ischemic neuronal tissues, where the thrombolytic motif is “switched‐on” by the action of thrombin. In mice and rat IS models, the PNzyme/MnO2 prolongs the blood‐circulation time and exhibits strong thrombolytic action, and reduces the ischemic damages in brain tissues. Moreover, this peptide‐templated nanozyme also effectively inhibits the activation of astrocytes and the secretion of proinflammatory cytokines. These data indicate that the rationally designed PNzyme/MnO2 nanozyme exerts both thrombolytic and neuroprotective actions. Giving its long half‐life in the blood and ability to target brain thrombi, the biocompatible nanozyme may serve as a novel therapeutic agent to improve the efficacy and prevent secondary thrombosis during the treatment of IS.
A peptide‐templated manganese dioxide nanozyme integrating thrombolytic and reactive oxygen species scavenging abilities is developed for the treatment of ischemic stroke. Through the self‐assembled polypeptides that contain multiple functional motifs, the nanozyme binds fibrin in the thrombus, crosses the blood–brain barrier, and finally accumulates in the ischemic neuronal tissues, where the thrombolytic motif is “switched‐on” by the action of thrombin.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nanozymes have great potential to be used as an alternative to natural enzymes in a variety of fields. However, low catalytic activity compared with natural enzymes limits their practical use. It is ...still challenging to design nanozymes comparable to their natural counterparts in terms of the specific activity. In this study, a surface engineering strategy is employed to improve the specific activity of Ru nanozymes using charge‐transferrable ligands such as polystyrene sulfonate (PSS). PSS‐modified Ru nanozyme exhibits a peroxidase‐like specific activity of up to 2820 U mg−1, which is twice that of horseradish peroxidase (1305 U mg−1). Mechanism studies suggest that PSS readily accepts negative charge from Ru, thus reducing the affinity between Ru and ·OH. Importantly, the modified Ru‐peroxidase nanozyme is successfully used to develop an immunoassay for human alpha‐fetoprotein and achieves a 140‐fold increase in detection sensitivity compared with traditional horseradish‐peroxidase‐based enzyme‐linked immunosorbent assay. Therefore, this work provides a feasible route to design nanozymes with high specific activity that meets the practical use as an alternative to natural enzymes.
Surface modification can engineer charge transfer between Ru and ligands and facilitate intermediate radicals to react with colorimetric substrate, which significantly improves the peroxidase‐like activity of Ru nanozymes superior to horseradish peroxidase. Following such a mechanism, polystyrene‐sulfonate‐modified Ru nanozymes can be used as an enzyme alternative in enzyme‐linked immunosorbent assay to improve detection sensitivity up to 140‐fold, validated with human alpha‐fetoprotein.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Protein‐protected metal nanoclusters (MNCs), typically consisting of several to a hundred metal atoms with a protein outer layer used for protecting clusters from aggregation, are excellent ...fluorescent labels for biomedical applications due to their extraordinary photoluminescence, facile synthesis and good biocompatibility. Interestingly, many protein‐protected MNCs have also been reported to exhibit intrinsic enzyme‐like activities, namely peroxidase, oxidase and catalase activities, and are consequently used for biological analysis and environmental treatment. These findings have extended the horizon of protein‐protected MNCs' properties as well as their application in various fields. Furthermore, in the field of nanozymes, protein‐protected MNCs have emerged as an outstanding new addition. Due to their ultra‐small size (<2 nm), they usually have higher catalytic activity, more suitable size for in vivo application, better biocompatibility and photoluminescence in comparison with large size nanozymes. In this review, we will systematically introduce the significant advances in this field and critically discuss the challenges that lie ahead. Ultra‐small nanozymes based on protein‐protected MNCs are on the verge of attracting great interest across various disciplines and will stimulate research in the fields of nanotechnology and biology.
This article is characterized under:
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures
Protein‐protected metal nanoclusters, while traditionally used as fluorescent labels, have recently emerged as an ultra‐small nanozyme (nanomaterials with intrinsic enzyme‐like activity), extending the horizon of their properties as well as their application in various fields.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
