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Multienzymes activity of metals and metal oxide nanomaterials: applications from biotechnology to medicine and environmental engineering


With the rapid advancement and progress of nanotechnology, nanomaterials with enzyme-like catalytic activity have fascinated the remarkable attention of researchers, due to their low cost, high operational stability, adjustable catalytic activity, and ease of recycling and reuse. Nanozymes can catalyze the same reactions as performed by enzymes in nature. In contrast the intrinsic shortcomings of natural enzymes such as high manufacturing cost, low operational stability, production complexity, harsh catalytic conditions and difficulties of recycling, did not limit their wide applications. The broad interest in enzymatic nanomaterial relies on their outstanding properties such as stability, high activity, and rigidity to harsh environments, long-term storage and easy preparation, which make them a convenient substitute instead of the native enzyme. These abilities make the nanozymes suitable for multiple applications in sensing and imaging, tissue engineering, environmental protection, satisfactory tumor diagnostic and therapeutic, because of distinguished properties compared with other artificial enzymes such as high biocompatibility, low toxicity, size dependent catalytic activities, large surface area for further bioconjugation or modification and also smart response to external stimuli. This review summarizes and highlights latest progress in applications of metal and metal oxide nanomaterials with enzyme/multienzyme mimicking activities. We cover the applications of sensing, cancer therapy, water treatment and anti-bacterial efficacy. We also put forward the current challenges and prospects in this research area, hoping to extension of this emerging field. In addition to therapeutic potential of nanozymes for disease prevention, their practical effects in diagnostics, to monitor the presence of SARS-CoV-2 and related biomarkers for future pandemics will be predicted.


Enzymes, as biological macromolecules, are mainly composed of proteins, which can efficiently and selectively catalyze a diverse biochemical reactions [1, 2]. They play a notable function in various fields, such as energy production processes, biosensing, the food industry, and biofuels [3,4,5,6]. However, they have some drawbacks, such as product complexity, harsh catalytic conditions and low operational stability because of digestion and denaturation. In addition, it has high costs in preparation and purification [7, 8]. To address these issues, nanomaterial with enzyme-like characteristics (nanozyme) was applied as a novel alternative candidate. Artificial enzymes have attracted the significant attention of researchers due to their higher stability, low cost, flexibility and tunable catalytic activities [9,10,11]. Compared with other artificial enzymes, nanozymes possess outstanding properties such as their size and structure dependent catalytic activities, multi enzyme activity, large surface area, smart response and self-assembly capability [12, 13]. On the basis of these outstanding properties, nanozymes have been widely utilized for disease diagnosis and treatment, chemical sensing, environmental protection and antibacterial agents [7, 14,15,16,17]. Up to now, lots of nanomaterials have been uncovered to mimic several natural enzymes, such as peroxidase, oxidase, catalase, superoxide dismutase (SOD), phosphatase, nuclease, esterase, protease and ferroxidase [18]. Since the finding of Fe3O4 nanoparticles as peroxidase mimics in 2007 [19], a large amount of studies on metal and metal oxide nanozymes have been reported. For example, Au, Pt, Pd, Co3O4, CeO2, CuO, MnO2, NiO, V2O5 nanocomposites have been shown to possess a unique enzyme-like property [20,21,22,23,24,25,26,27,28]. Metal and metal oxide nanomaterial played great role in progress and development of enzyme mimic technology, due to their unique combination of redox chemistry, optical and electrical properties [29,30,31,32]. Interestingly, some nanomaterial can mimic the function of two or three enzymes. It has been reported that the simultaneous expression of multiple enzymes is more effective than single expression to remove harmful reactive oxygen species [33]. When designing a cascade reaction, it is often appropriate to use multiple nanozyme as the cascade catalyst. In this review, we present a comprehensive review of applications of metal and metal oxide nanozyme in terms of chemical sensing and biosensing, cancer treatment, water purification and anti-bacterial efficiency (Table 1). We also highlight some recent examples of multi-enzyme applications in catalysis. Because of the space limit, we could not cover all the related publications. However, we summarize recent research works on metal and metal oxide based nanozyme in Table 1. In the last section, the current challenges and future opportunities of metal and metal oxide-based nanozymes are also discussed. We hope that the present review will be of great benefit for development of novel nanozymes in the fields of medicine, chemistry, biology and nanotechnology.

Table 1 Current metal and metal oxide nanozymes, their typical applications and representative references

Nanozymes for sensing application

Metal and metal oxide-based nanozymes with substantial properties have been widely applied for several analytical purposes. The principle detection is divided into two categories: (1) the target activates or deactivates a reaction between the nanozyme and the agent, (2) the presence of the nanozyme and its reaction with the agent indirectly indicates the amount of target. According to previous reports, the application of such nanozymes includes detection of a variety of important targets, such as tumor markers, small biomolecules and metal ions [18, 28, 34].

Tumor markers

Synthesize nanomaterials within cage-like protein templates has been demonstrated to be a suitable approach to produce uniform [35]. Ferritin nanocages provide surface modification and specific targeting abilities for synthesizing ferritin-based nanozymes [36]. Biomineralization synthesis of cobalt nanozyme in SP94-ferritin nanocage was reported for prognostic diagnosis of hepatocellular carcinoma (HCC) [37]. In this report, ferritin-based cobalt nanozyme (HccFn(Co3O4)) was designed for HCC diagnosis and therapy. SP94 peptide was modified onto the exterior surface of ferritin nanocage (HccFn) for specifically binding to HCC cells. HccFn(Co3O4) nanozymes specifically bound to HCC tissues and catalyze the oxidation of peroxidase substrate diaminobenzidine (DAB) to produce deep brown colorimetric reaction. In comparison with Fn(Co3O4) control group, HccFn(Co3O4) nanozymes specifically recognized and visualized HCC tissues and could distinguish tumor cells from normal tissues (Fig. 1).

Fig. 1

HccFn(Co3O4) nanozymes specifically recognize and visualize clinical HCC tissues. a HccFn(Co3O4) nanozymes showed peroxidase-like activity and catalyzed the oxidation of peroxidase substrate diaminobenzidine (DAB) to produce colorimetric reaction. b Schematic diagram of HccFn(Co3O4)-based immunohistochemical approach. c HccFn(Co3O4)-based immunohistochemical staining (top row) and Fn(Co3O4)-based immunohistochemical staining (bottom row) of HCC tissues and non-tumor liver tissues

The nanomaterial-mediated colorimetric sensor is an attractive system for advance instrument-free bioanalysis due to its unique advantages of simplicity in operating analysis via camera or smartphone [38, 39]. Several colorimetric assays based on the 3,3,5,5 tetramethylbenzidine (TMB)-H2O2 system catalyzed by enzyme mimic nanomaterials have been extensively developed for immunoassay [40,41,42]. For instance, Alizadeh et al. present a paper-based microfluidic colorimetric immunosensor for the detection of carcinoembryonic antigen (CEA), using Co2(OH)2CO3-CeO2 nanocomposite with extraordinary intrinsic peroxidase like activity [43]. The proposed immunosensor facilely prepared by modifying mixture of ionic liquid and chitosan functionalized primary antibodies (Ab1) on the surface of paper. Co2(OH)2CO3-CeO2 peroxidase mimicking enzyme was functionalized secondary antibodies (Ab2) and used as a signal tag. Co2(OH)2CO3–CeO2 nanocomposite catalyzed the oxidation of 3,3′,5,5′-tetramethyl benzidine in the presence of H2O2, resulting in a color change, which acquired as the immunosensor response. The color change was distinct by the naked eye and analyzed by an installed application on the smartphone (Fig. 2).

Fig. 2

Schematic illustration and assay procedure of CEA detection on the paper-based chip

In colorimetric assays, color changes and photothermal effect of TMB-H2O2 colorimetric system have been prospected [44]. In this regard, nanoparticle (NPs)-mediated photothermal immunoassay platform was developed for detection of prostate-specific antigen (PSA) using a common thermometer as the quantitative signal reader [45]. The iron oxide NPs-labeled antibody was applied as the detection probe, on basis of sandwich-type proof-of-concept immunoassay. In the immunoassay, iron oxide artificial enzyme demonstrated color changes and also a strong NIR laser-driven photothermal effect, simultaneously. The oxidized TMB acted as a highly sensitive photothermal probe to convert the immunoassay signal into heat via its photothermal effect (Fig. 3).

Fig. 3

Schematic illustration of the photothermal immunoassay platform based on the photothermal effect of the iron oxide NPs mediated TMB-H2O2 colorimetric system

Aptamers are artificial synthetic single-stranded DNA or RNA oligonucleotides, which can bind with various targets such as protein, peptide, organic/inorganic molecule, and cell with high affinity and specificity. Aptamer with superiority to antibodies, including high stability, ease of synthesis, low cost and easy chemical modification, have attracted a lot of attention in biomedical and bioanalysis research [46,47,48]. Zhao et al. selected three hairpin anti-MUC1 DNA aptamers for construction of a sensitive electrochemical aptasensor based on catalytic hairpin assembly coupled with PtPdNPs peroxidase-like activity [49]. After binding with target protein, Apt-HP1 containing aptamer sequence was opened and MUC1-aptamer binding complex formed (Fig. 4). Next, the exposed segment of HP1 would attack HP2 immobilized on the electrode to form a double strand structure. Then, the new exposed segment of HP2 hybridized with the toehold of PtPdNPs modified HP3. Finally, MUC1-A was released via the strand displacement process, and the released MUC1-A could participate in the subsequent reaction cycles. The carried PtPdNPs, as a mimic peroxidase probe, catalyzed the TMB by H2O2, leading to the electrochemical signal generation.

Fig. 4

Schematic representation of the aptasensor for the detection of MUC1

Metal ions

Most studies on metal ions sensing with nanozymes have been devoted to mercury ions (Hg2+) [9, 50, 51]. Mercury is a toxic metal ion that in the environment can produce several harmful effects on people`s health like brain, heart, kidneys and central nervous system damages [52, 53]. Through the bacteria action in a lake and ocean, Hg2+ converts into more toxic organic mercury and accumulates in aquatic organisms [54]. Thereupon, it can accumulate continuously in the body through water and food. In a report, dual colorimetric and SERS detection of Hg2+ was developed based on the stimulus of intrinsic oxidase-like catalytic activity of Ag-CoFe2O4/rGO nanocomposites [55]. CoFe2O4 nanoparticles in Ag-CoFe2O4/rGO nanocomposites exhibited an oxidase-like activity, which can quickly catalyze the oxidation of typical chromogenic substrates 3,3ʹ,5,5ʹ-tetramethylbenzidine (TMB) in the presence of dissolved oxygen. The introduction of Hg2+ led to enhancement in oxidase-like activity of the Ag-CoFe2O4/rGO nanocomposites due to the formation of the Ag-Hg alloy. Owing to the existence of the Ag nanoparticles the prepared nanocomposites have also been demonstrated to be efficient SERS substrate. In another report, colorimetric detection of Hg2+ in various groundwater samples was successfully performed using CuO/ Pt Nanoflowers (NFs). In the presence of Hg2+, the peroxidase activity of CuO/Pt NFs was hindered, because the formation of the CuO/Pt-Hg trimetallic amalgam [56].

Lead (Pb2+) is known as a non-biodegradable, toxic and perdurable metal ion. It has a strong negative effect on children’s behavior and serious damage to the brain, immune system of many life tissues including liver, brain, kidney and also immune and central nervous system [57,58,59]. Xu et al. reported colorimetric and electrochemiluminescence dual mode sensing of lead ion biomolecules using graphene oxide (rGO)-PdAu probe [60]. Pb2+-specific DNAzyme was immobilized onto rGO-PdAu-glucose oxidase (GOx). The thiol modified Pb2+-dependent DNAzyme was self-assembled onto the surface of the flower-like Au NPs modified ECL detection zone to hybridize with rGO-PdAu-GOx labeled oligonucleotide. Upon introducing of Pb2+ into the prepared system, the double helix structure of DNA was cleaved, resulting in the release of rGO-PdAu-GOx probe to catalyze the oxidation and color change of TMB. Meanwhile, the concentration of H2O2 is proportional to the luminol ECL system, which constitutes a new mechanism for ECL detection of Pb2+ (Fig. 5).

Fig. 5

Schematic representation of fabrication procedures of the lab-on-paper device and dual mode sensing mechanism

Inspired by the aggregation-induced emission (AIE) properties, the catalytic activity of metal nanozyme could be altered upon aggregation, because both optical and catalytic properties of metal nanocomposites are highly dependent on their size and morphology. It was found that the Pb2+-induced aggregation can greatly accelerate the peroxidase-like activity of Au nanoclusters (Au-NCs) [61]. In the absence of Pb2+, Au-NCs could catalyze the TMB oxidation by H2O2 in a relatively slow reaction rate. After the Pb2+-induced aggregation, the peroxidase activities of Au-NCs toward oxidation of TMB substrate in the presence of H2O2 are nearly tenfold increased.

Some cascade reactions were configured between enzyme-like nanomaterials and natural enzymes [62, 63]. This cascade catalytic system must be carried out in two steps, because the optimal pH conditions for each enzyme is different. To address the limitation of different conditions, a single nanomaterial with dual activity has been constructed to mimic enzyme cascade reaction [64]. He et al. described a self-cascade system based on cupric oxide nanoparticles as dual-functional enzyme mimics for ultrasensitive detection of silver ions [65]. Cupric oxide nanoparticles (CuO NPs), as the dual-functional nanozyme, demonstrated the intrinsic GSH-oxidase and peroxidase-like activity coupling with terephthalic acid (TA) and GSH to construct a self-cascade fluorescent system. CuO NPs effectively catalyze the oxidation of GSH by oxygen to produce glutathiol (GSSG) and hydrogen peroxide, following to catalyze the decomposition of hydrogen peroxide into hydroxyl. Then, a highly fluorescent product TAOH was formed by oxidation of terephthalic acid (TA) in the presence of hydroxyl radical. Thus, in the presence of GSH, the turn-on fluorescence signal of oxidation hydroxyterephthalate (TAOH) is created. Introduction of the Ag+ ions cause to inhibition of the fluorescence of H2O2-TA-CuO NPs reaction system. It is due to that Ag+ ions can react with the H2O2 intermediate product resulted from the oxidation of GSH.

Until now, many assays for single heavy metal ions have been reported [66,67,68]. However, some efforts have been made to develop simultaneous detection of metal ions. Hg2+ and Ag+ are usually coexisting in water, soil and even biological systems [69]. Peng et al. prepared core–shell Au@Pt nanoparticles for simultaneous colorimetric detection of Hg2+ and Ag+ [70]. Both Hg2+ and Ag+ were found to intensively inhibit the catalytic activity of Au@Pt NPs. The complexation of sodium dodecyl sulfate (SDS) shields interference metal ions such as Mn2+, Sr2+, Zn2+, Fe3+, Co2+, Cu2+ and Bi3+, to obtain specific respond of Hg2+ and Ag+. As well as, L-cysteine can be used to mask Hg2+ in the presence of Ag+. In another study, Colorimetric detection of Hg2+ and Pb2+ was achieved based on peroxidase-like activity of graphene oxide–gold (GO–AuNP) nanohybrids [71]. Single-stranded DNA (ssDNA) were stable against the salt-induced aggregation of GO–AuNP nanohybrids, whereas double stranded DNA (dsDNA) did not hinder salt-induced GO–AuNP nanohybrids aggregation. On the basis of the ability of GO–AuNP nanohybrids to differentiate between ssDNA and dsDNA, label-free colorimetric method for the detection of Hg2+ and Pb2+ was developed. With addition of Hg2+ or Pb2+, ssDNA formed a hairpin-like or a quadruplex structure, and these conformational changes led to the salt-induced aggregation of GO AuNP nanohybrids. After addition of TMB and H2O2, the colorimetric signal was significantly decreased compared to that in the absence of Hg2+ or Pb2+.


Glucose is the main energy source for cellular metabolism and function of human bodies. However, people with glucose excessive suffer from diabetes mellitus. Diabetes can cause serious health problems, such as strokes, heart attacks, high blood pressure, and even blindness or death [72, 73]. Guo and co-workers fabricated Ag-Cu2O/reduced graphene oxide nanocomposites with peroxidase-like catalytic reaction for (Surface-enhanced Raman spectroscopy) SERS detection of glucose [74]. SERS facilitate highly sensitive and selective identification of analytes such as glucose. Ag-Cu2O/rGO nanocomposites operate as both peroxidase nanozyme and SERS substrates; they speed up the reaction between TMB and H2O2. A SERS method has been designed based on the ability of glucose oxidase (GOx) to catalyze the oxidation of glucose to gluconolactone and H2O2. In this method, glucose was determined by the catalytic oxidation of TMB in the presence of GOx and glucose. Discern between diabetic and normal individuals by determining the glucose levels within a fingerprint is the most important feature of this work (Fig. 6).

Fig. 6

SERS spectra of oxidized TMB molecules on the surface of fingerprint from diabetes patients and normal pers in the presence of Ag-Cu2O/rGO substrates and GOx. The bottom line is blank test without fingerprint. On the right is schematic representation of SERS detection of fingerprint by using Ag-Cu2O/rGO nanocomposites as SERS substrate

Ascorbic acid (AA) neurochemicals, used as an enzyme cofactor and antioxidant. Meanwhile, AA plays a critical role of anti-oxygenation and resists the cells damage from free radicals. High level of AA can selectively kill colorectal cancer cells as a pro-oxidant anticancer agent [75, 76]. Therefore, methods for simple, fast, and effective AA assay suitable for the biological systems are required. Ding et al. the CoOOH-TMB oxidative system for colorimetric and test strip based detection of ascorbic acid [77]. CoOOH nanoflakes directly oxidize TMB (colorless) to blue oxTMB with a characteristic absorption peak at 652 nm. In the presence of ascorbic acid (AA), the absorbance decreased because AA reduces oxTMB. Furthermore, the CoOOH-TMB systems can be further developed into a paper-strip-based assay for determination of AA in rat brain (Fig. 7).

Fig. 7

Schematic of colorimetric assay mechanism and platform for the detection of AA in rat brain by the CoOOHTMB system

By reacting with H2O2, some small bioactive molecules like dopamine and glutathione (GSH) have been determined based on their inhibition effects on peroxidase enzyme mimics [78, 79]. For example, GSH in human serum samples was determined using FeMnO3 nanoparticles-filled polypyrrole nanotubes as peroxidase mimic [80]. More, with Yang's sensing strategy, selective colorimetric detection of dopamine was successfully executed in real samples [81].

Cancer cell and bacteria

Cancer is one of the fatal sicknesses and has become a major public worry in the world [82]. Presently, early diagnosis has been made to be the most effective way to raise survival rate [83]. Thus, it is highly needed to develop sensitive, rapid and specific methods to detect and quantification of cancer cells at early stage [84]. The conjugation of aptamer or a ligand with nanozymes can be employed for cancer cells detection. For instance, MCF-7 circulating tumor cells were detected by an electrochemical cytosensor with effective surface recognition between specific mucin 1 protein (MUC-1) over-expressed on the MCF-7 cell membranes and MUC-1 aptamer [85]. The CuO nanozyme was used as a signal-amplifying nanoprobe with reduced graphene oxide/gold nanoparticles composites (rGO/AuNPs composites) as a support material (Fig. 8I). The fabricated “sandwich” structure can help to reach on the acceptable sensitivity of the proposed cytosensor.

Fig. 8

Schematic representation of the cytosensor for detection of MCF-7 using (I) CuO and (II) Fe3O4 nanozyme

The immunomagnetic sensor was also developed for electrochemical detection of MCF-7 circulating tumor cells [86]. Fe3O4 NPs magnetic beads act as both separation and enrichment CTCs and as enzyme mimics with rGO/MoS2 synergistic catalysis (Fig. 8II). The CTCs could be separated and enriched on the magnetic glassy carbon electrode (MGCE) by Fe3O4 NPs coated aptamer. Electrochemical current of TMB redox product was generated via Fe3O4 NPs/rGO/MoS2 catalytic ability.

Recently, several studies reported that folate-modified nanozymes could detect cancer cells with over-expressed folate receptor [87,88,89,90]. In Alizadeh and co-workers' study, the novel method was developed for electrochemical cancer cell detection using CuO/WO3 nanoparticle decorated graphene oxide nanosheet (CuO/WO3-GO) conjugated with folic acid (FA) [91]. In the absence of cancer cells, o-Phenylenediamine (OPD) oxidized on the Au electrode in the presence of H2O2, while FA/CuO/WO3-GO with peroxidase like activity reacted with folate receptor of cancer cells seeded on 96-well plate, catalyzed the oxidation of OPD in presence of H2O2 (Fig. 9). Actually, in the presence of cancer cells, the response signal decreased, because some amount of H2O2–OPD system participated in chemical reaction and removed from the electrode. In this way, cancer cells detected in wide linear range and a low detection limit.

Fig. 9

Schematic illustration of obtained chemical /electrochemical reactions and peroxidase activity of CuO/WO3-GO for cancer cell detection

Infectious diseases induced by bacteria considered a cause of more than 25% of all global deaths [92]. Pathogen detection is an important step in the inhibition of these types of infectious and deadly diseases [93]. Several studies have been employed for bacteria detection using nanozymes as probing elements [94,95,96]. Recently, Cheng et al. reported nanozyme mediated dual-immunoassay integrated with smartphone for use in simultaneous detection of pathogens [97]. They applied platinum-palladium (Pt–Pd) nanoparticles as a signal amplifier in a dual-lateral flow immunoassays (LFIA) and for simultaneous colorimetric detection of Salmonella Enteritidis and E. coli O157:H7. Smartphone-based device and its ability to image provide a portable and cost-effective platform for tracking bacterial contamination along the entire food chain.

Nanozymes for therapeutics application

Reactive oxygen species (ROS), is a general expression that describes the chemical species generated upon incomplete reduction of oxygen [98]. ROS including hydrogen peroxide, superoxide anion, hydroxyl radical and singlet oxygen have the potential to kill cancer cells by destroying biomolecules such as DNA, proteins and lipids [99]. In recent years, substantial achievements have been made in ROS-based nanomedicine, especially in cancer and bacterial infection [100,101,102]. The development of nanotechnology has favored the production of several ROS-generation materials with enzyme-mimic characteristics [103]. Metal and metal oxide nanozymes with peroxidase- and catalase- like activities, can convert endogenous biological H2O2 into highly cytotoxic OH· and O2·– species [104]. Furthermore, developing nanotechnology and nanozymes with special ROS-regulating properties solve the problem of the instability of ROS-based therapeutics. In this section, nanozymes catalytic mediated cancer therapies are discussed, which cover (photodynamic therapy) PDT, chemodynamic therapy (CDT), sonodynamic therapy (SDT) and photothermal therapy (PTT). Furthermore, the Metal and metal oxide-based nanozymes for antimicrobial therapies are summarized.

Chemodynamic therapy (CDT)

Chemodynamic therapy (CDT) is an emerging cancer treatment strategy that damage tumor cells with a localized Fenton reaction. In CDT process iron mediated Fenton reaction induces intracellular oxidative stress by converting less reactive H2O2 into OH·, one of the most detrimental ROS [105, 106]. Up to now, iron oxide and other metal oxide nanocomposite enzyme mimic are capable of decomposing H2O2 into OH· through Fenton-like reactions [107]. Researchers have been widely studied CDT treatment method because of its high tumor specificity, lower side effects and minimal invasiveness. Generally, transition metal ions (e.g., Fe, Co, Ni, Cu, and Mn) used as the CDT agents to catalyze the decomposition of hydrogen peroxide (H2O2) and produce high-toxicity hydroxyl radicals (·OH) (Typical reaction: Fe2+  + H2O2 → Fe3+  + ·OH + OH). Biomolecular substances including nucleic acids, lipids and proteins in tumor cells are destroyed as a result of oxidative stress [108, 109]. Conceivably, some challenges like overexpressed glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) in tumor cells, low H2O2 concentration and requirement of strong acidic chemical environment obstacles CDT. Lin et al. reported enhanced chemodynamic therapy based on MnO2 nanoagent with Fenton-like Mn2+ delivery and GSH depletion properties [110]. The MnO2 was established on the surface of thiol-functionalized mesoporous silica (MS) NPs, leading to the formation of MnO2-coated MS NPs (MS@MnO2 NPs). Upon uptake of the MS@MnO2 NPs by cancer cells, the MnO2 layer would simultaneously release Mn2+ with superior Fenton-like activity to transform endogenous H2O2 produced into the highly toxic OH· and deplete intracellular GSH to inhibit OH· scavenging (Fig. 10a, b). As well as, the potential of MnO2 shell as a gatekeeper for controlled drug release showed by loading hydrophobic anticancer drug camptothecin (CPT) into the PEGylated MS@MnO2 NPs. Hematoxylin and eosin (H&E)-stained images demonstrated that tumor tissues treated with MS@MnO2-CPT suffered more intense damage than other control group, which indicates enhanced chemodynamic efficacy of MS@MnO2-CPT for theranostic applications (Fig. 10c).

Fig. 10

a The mechanism of MnO2 as a smart chemodynamic agent for enhanced CDT of cancer. Upon endocytosis, the MnO2 can react with intracellular GSH to produce GSSG and Mn2+, which exerts excellent Fenton-like activity to generate highly reactive OH· from endogenous H2O2 in the presence of physiological HCO3-. The impairment of antioxidant defense system (ADS) resulting from GSH depletion makes cancer cells more vulnerable to OH· formed in Mn2+-mediated Fenton-like process, enabling enhanced CDT. b Schematic illustrating the application of MS@MnO2 NPs for MRI-monitored chemo-chemodynamic combination therapy. c H&E-stained images of tumor sections from different groups. Scale bar, 100 μm

Until now, almost all developed CDT agents are acidity dependent (optimum Fenton reaction pH: 2–4) and a few studies have been carried out to develop wide pH range-responsive CDT agents [111]. However, the neutral-pH conditions at the solid tumor surface resulting from abundant vessel distribution and sufficient oxygen supply undo the effect of acidity-activated nanoagents and even induce tumor recurrence and metastasis after treatment [112, 113]. Zhaoʼs group synthesized Ferrous-cysteine–phosphotungstate nanoagent for enhanced cancer chemodynamic therapy that breaks through the limitation of a neutral pH [114]. The advantages from the addition of phosphotungstate and cysteine to formation of a Fe3+ chelating complex inhibited the formation of inert Fe(OH)x, and accelerate electron transfer between ferric and ferrous ions, respectively (Fig. 11a).

Fig. 11

a Schematic illustrating the synthesis process and mechanism for FcPWNP mediated pH independent high efficiency CDT, b ESR spectra of different groups treated with DMPO; FcPWNPs: Fe concentration of 80 ppm, and H2O2: 1 mM. c The growth inhibition effect on 4T1 cells of different groups after 24 h of incubation. (Fe element: 40 ppm, H2O2: 200, 100 and 50 mM, pH 7.4, 6.5 and 5.4). (n = 6, mean ± SD)

To investigate the OH· generation ability of the ferrouscysteine–phosphotungstate nanoparticles (FcPWNPs), electron spin resonance (ESR) spectroscopy is conducted. As can be seen in Fig. 11b, FcPWNPs show representative hydroxyl radicals with pH-dependent tendency. The strong cytotoxicity against cancer cells with an H2O2 dose-dependent tendency was achieved inspired by the high OH· production performance across a wide pH range, (Fig. 11c).

Although, compared with normal cells, many types of tumor cells have higher intracellular H2O2 levels, the endogenously generated H2O2 is still inadequate to obtain improved CDT efficacy [115]. Thereafter, their anticancer efficiency could be enhanced by the introduction of H2O2-supplementing functionality into CDT agents. Lin et al. developed copper peroxide nanodots for H2O2 self-supplying chemodynamic therapy [116]. Copper peroxide CP nanodots were prepared through the binding of H2O2 to Cu2+ in the presence of poly (vinylpyrrolidone) (PVP) as stabilizer at room temperature. This Fenton-type peroxide nanomaterial utilized as an activatable agent for enhanced CDT by self-supplying H2O2 (Fig. 12a). Upon acid treatment, the reversible decomposition of CP nanodots into Fenton catalytic Cu2+ and H2O2 occurred.

Fig. 12

a Formation of CP Nanodots for H2O2 Self-Supplying CDT, b Fluorescence images of DCFH-DA-stained U87MG cancer cells after exposure to different concentrations of CP nanodots for 4 h. The scale bar represents 50 μm

2′,7′-dichlorofluorescin diacetate (DCFHDA), the fluorescent ROS indicator, was applied to evaluate the production of OH· by CP nanodots at the cellular level. Deacetylation of DCFH-DA and formation of nonfluorescent DCFH was accomplished by intracellular esterases, which can be oxidized by ROS and then emits green fluorescence [117]. It was shown in Fig. 12.B that U87MG cancer cells incubated with CP nanodots exhibited significantly higher green fluorescence than untreated control cells, indicating the ability of CP nanodots to generate OH· within tumor cells.

Therapeutic selectivity, characteristic differences between healthy and cancer cells, is one of the critical factors in development of cancer therapies. Due to rapidly proliferating, cancer cells have high H2O2 levels with a low catalase level in comparison with normal cells. In this regard, SnFe2O4 nanocrystals were employed for selective killing of lung cancer cells by catalase-modulating heterogeneous Fenton reaction [118]. A working mechanism of this developed assay is the inhibition of the heterogeneous Fenton reaction in normal cells with catalase through decomposition of H2O2 (Fig. 13a). Furthermore, the sonicated SnFe2O4 nanocrystals demonstrated much higher efficiency than the non-sonicated nanocrystals to produce the hydroxyl radicals. Therefore, the sonicated SnFe2O4 nanocrystals in presence of catalase exhibited low cell viability compared with test cells treated with non-sonicated nanocrystals without catalase (Fig. 13b).

Fig. 13

a Illustration showing internalized SnFe2O4 nanocrystals performing cytotoxic effect on cancer cells intracellularly and non-cytotoxic effect on cancer cells in presence of catalase. b Fluorescent images of slices co-stained with LIVE(green)/DEAD(red), viability/cytotoxicity assay kit for test cells

In cancer therapy, DOX can activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) for transportation of electrons across the membrane. The activated NOXs can catalyze NADPH into NADP+ along with the release of electrons. Thus, the oxygen captures the electrons to produce the superoxide anion radical (O2·) and afterward product the H2O2 by disproportionation reaction with superoxide dismutase (SOD) enzyme [119,120,121]. In Fenton reactions, iron oxide core–shell mesoporous silica (Fe3O4@MSN) nanocarrier promoted oxygen species levels reactive for cancer therapy [122]. Fe3O4@MSN-TPP/PEG-FA was formed by conjugation of Fe3O4@MSN with folate (PEG-FA) and mitochondrial targeting triphenylphosphonium (TPP). Then, Fe3O4@MSN-TPP/PEG-FA encapsulated doxorubicin (DOX) and 3-amino-1,2,4-triazole (AT) for cancer therapy (Fig. 14I). AT, as a catalase inhibitor inhibits the catalase activity to save the production of H2O2. The assessment of ROS level induced by DOX/AT-loaded Fe3O4@MSN-TPP/PEG-FA in MCF-7 and MGC-803 cells showed that green fluorescence was gradually improved after different incubation times (Fig. 14II). The results proved the significant elevation of the intracellular ROS level stimulated by DOX/AT-loaded Fe3O4@MSN-TPP/PEG-FA.

Fig. 14

I The DOX/AT loaded Fe3O4@MSN-TPP/PEG-FA accumulated in the tumor cells by recognition of folate receptors and further targeted to mitochondria by TPP-mediated effect. In this study, excessively toxic OH· which could induce cell death were generated by a series of biochemical reactions. II Evaluation of ROS generating capability of DOX/AT-loaded Fe3O4@MSN-TPP/PEG-FA in vitro. (A) CLSM images of MCF-7 and MGC-803 cells incubated with DOX/AT-loaded Fe3O4@MSN-TPP/PEG-FA for different incubation time. Flow cytometry assay ROS level of MCF-7 cells (B) and MGC-803 cells (C). a, control group; b, DOX/AT-loaded MSN-TPP/PEG-FA; c, DOX/AT-loaded Fe3O4@MSN; d, DOX/AT-loaded Fe3O4@MSN-TPP/PEG-FA. (D) The analysis of flow cytometry. (n = 3). *P < 0.05 and **P < 0.01

Photodynamic therapy (PDT)

Photodynamic therapy (PDT) is the most versatile minimal invasive manner of cancer therapy, which involves the production of cytotoxic reactive oxygen species (ROS) by light activation of photosensitizers [123, 124]. The produced ROS induce cell apoptosis or necrosis, microvascular damage and immune responses. Aggressive proliferation of cancer cells and an insufficient blood supply in tumors decrease O2 concentration. The O2 deficiency in tumors leads to a significantly reduced antitumor efficacy of PDT [125,126,127]. In PDT, O2 employs to produce ROS, so, hypoxia obviously arises during PDT. Hypoxia, yielded from the imbalance between oxygen supply and consumption, is a great indicator of cancer progression. Since, O2 is a necessary component in PDT and hypoxia prevents effective cancer treatments [128, 129]. In view of this, tremendous attention has been attracted to overcome tumor hypoxia. Recently, various nanomaterials with catalase like activity, have been employed to catalytically generate O2 to mitigate cancer hypoxia. For example, manganese ferrite nanoparticle-anchored mesoporous silica nanoparticles to eliminate hypoxia and efficient photodynamic therapy [130]. Manganese ferrite nanoparticles (MFNs) act as a Fenton catalyst for decomposition of H2O2 and continuous O2 generation. The level of hypoxia can be examined based on HIF-1α amounts, because hypoxia-inducible factor (HIF-1α) protein is adjusted under hypoxic condition [131]. As can be seen in Fig. 15, when the cancer cells were treated with manganese ferrite nanoparticle-anchored mesoporous silica nanoparticles (MFMSNs), the fluorescence intensity of HIF-1α has decreased in concentration dependent manner, suggesting the capability of MFMSNs to reducing hypoxia via O2 production after cellular uptake.

Fig. 15

a Schematic illustration of MFMSNs. b CLSM images of HIF-1α (green) and F-actin (red) in cells incubated with MFMSN under normoxic or hypoxic condition, and c corresponding fluorescence intensity (n = 3). Scale bar, 20 μm. **P < 0.01

In another study, Zhang et al. used MnO2 nanodots to promote dissolved oxygen concentration and overcome hypoxia limitations [132]. The PDT nanoplatform is fabricated by one-pot encapsulating g-C3N4 and DOX in ZIF-8, then loading MnO2 nanodots and surface-modifying F127 (F127-MnO2-ZIF@DOX/C3N4, donated as FMZ/DC). F127 with excellent biocompatibility and amphiphilic nature is chosen as a stabilizing agent. Encapsulation into pH-dependent ZIF-8 carrier reduces the side effects of DOX induced by nonspecific drug release. In addition, g-C3N4, a prominent visible-light photocatalyst, could efficiently generate ROS and kill cancer cells (Fig. 16a, b). The efficacy of the tested materials to the living body was confirmed by measuring the tumor sizes of mice during the healing process (Fig. 16c, d).

Fig. 16

a Schematic illustration of the fabrication of FMZ/DC nanocomposites. The diagram is not drawn to scale. b Schematic illustration of FMZ/DC with oxygen generation enhancing the chemo-photodynamic therapy under 660 nm light irradiation. In vivo combination therapy of FMZ/DC by intravenous administration into a 4T1 tumor mouse model. c Tumor growth curves of different groups of 4T1 tumor-bearing mice. The laser irradiation (+ L) was carried out under 660 nm light at the power density of 5 mW cm − 2 for 30 min. Error bars were based on five mice in each group. d Images of tumors collected from different groups of mice 14 d after different treatment: a control; B DOX; C, Z/DC (− L); d FMZ/DC (− L); e Z/DC (+ L); f FMZ/DC (+ L)

MnO2 biomimetic nanozyme could be integrated glucose oxidase (GOx) enzyme for improved starvation and photodynamic therapy [133]. GOx can oxidize glucose to gluconic acid and H2O2, which is capable of tumor starvation therapy. Meanwhile, MnO2 accelerated O2 production with the aid of a large amount of H+ from oxidation product gluconic acid. This O2 supply decreases tumor hypoxia and promotes PDT effectiveness (Fig. 17).

Fig. 17

The scheme of MnO2-GOx hybrid achieving self-supplied H+ and accelerating O2 generation for alleviating tumor hypoxia and enhancing PDT and starvation therapy against hypoxic tumors

To achieve more stability and hinder the aggregation of small size mimicking enzyme nanoparticles, Zhangʼs group decorated Pt nanozymes on photosensitizers integrated MOFs for enhanced photodynamic therapy [134]. Pt nanoparticles with catalase like activity were decorated on porous coordination network-224 (PCN-224). The PCN-224-Pt could assist the formation of 1O2 in hypoxic tumor site via decomposition of H2O2 for producing O2, which could be employed for enhanced photodynamic therapy (Fig. 18I). Decreased in immonufluorescence intensity of HIF-1α for treated tumor slices with PCN-224-Pt indicated remove the hypoxia limitation by Pt NPs on PCN-224-Pt (Fig. 1). In the case of tumors of mice injected with PCN-224, tumor growth was completely inhibited after irradiation treatment (Fig. 18II).

Fig. 18

I Schematic illustration of (A) the preparation process of PCN-224-Pt and (B) the use of PCN-224-Pt for enhanced photodynamic therapy, II Photodynamic therapy of PCN-224-Pt by intratumoral injection in a subcutaneous tumor model. A) HIF-1α staining of tumor tissues collected from mice in different groups. B) Photographs of the H22 tumor-bearing mice before treatment and on day 14 after the various treatments. C) Representative photographs of the tumor dissection. D) Relative tumor volume after various treatments indicated. Asterisks indicate significant differences (*P < 0.05, **P < 0.01, ***P < 0.001)

It is reported that the activities of enzyme mimics are correlated with their nanostructures [135]. For instance, MoO3 − x nanourchins (NUs) exhibited a structure-dependent enzymatic activity with therapeutic effect in tumor microenvironment via cascade catalytic reactions [136]. In this design, MoO3 − x NUs possess high proportion of active MoV atoms and large active surface area, induce catalase (CAT)-like activity to produce a large amount of O2 for subsequent oxidase (OXD)-like reactivity (Fig. 19). The reactivity of MoO3 − x NUs in acidic PBS is much higher than that in neutral or alkaline; thus, MoO3 − x NUs would rapidly lose the enzymatic activity and leave normal tissues unharmed in a physiological environment (pH 7.4).

Fig. 19

Schematic Illustration of Biodegradation-Medicated Enzymatic Activity-Tunable Molybdenum Oxide Nanourchins (MoO3 − x NUs) with the Highly Specific Toxicity to Tumor Tissues via a Multienzyme Stepwise Cascade Catalysis in Acidic Tumor Microenvironment

Photothermal therapy (PTT)

Photothermal therapy (PTT) is a treatment modality with minimum side effects, which involves the artificial elevation of the tissue temperature. PTT agents capture near-infrared (NIR) light and convert it into heat, causing tumor cells apoptosis [137,138,139]. Without any laser exposure,

PTT agents are nontoxic and relatively safe to cells. In compare with traditional tumor treatment models including radiotherapy, surgery, and chemotherapy, PTT is attractive because of certain advantages, such as reduced invasiveness and high specificity [140, 141]. Nevertheless, tumor cells usually cannot be completely killed by photothermal treatment alone, finally resulting in tumor recurrence [142]. Thus, to further enhance the therapeutic performance of PTT, the enzyme-mimicking performance of nanozymes can be employed.

Au nanoparticles (Au NPs) are one of the most widely studied photothermal agents owing to their effective local heating upon excitation of surface plasmon oscillations. Besides, many studies displayed that Au NPs possess enzyme-like activities [143]. In this regard, Fanʼs group utilized yolk-shell gold@carbon nanozymes Tumor catalytic-photothermal therapy [144]. A hollow carbon nanospheres with porous shell (Au@HCNs) exhibited high oxidase-like and peroxidase-like activity enzyme activities. Meanwhile, Au@HCNs outstanding near-infrared light (NIR) absorbing agents for convert light into heat for tumor photothermal therapy (PTT). The enzyme-mimicking functions significantly improved by the photothermal effect, leading to large amounts production of ROS to destruct cancer cells. Tumor mice have been exposed with different groups of agents with or without NIR irradiation. The results showed that the tumors treated with Au@HCNs under 808-nm laser irradiation were completely destroyed without recurrence during the treatment (Fig. 20).

Fig. 20

In vivo catalytic-photothermal therapy of CT26 tumor bearing mice. a IR thermal images of CT26 tumor-bear mice with the NIR laser irradiation (808 nm, 2.0 W/cm2, 10 min) after intravenous injection with PBS, HCNs and Au@HCNs. b Tumor growth curves of different groups after treatment. c The body weight after various treatments during 21 days. d Photos of tumors from (1) control, (2) HCNs, (3) Au@HCNs, (4) HCNs + Laser, (5) Au@HCNs + Laser. e The Tumor weight after 21 days of treatment. f Representative photos of tumors on mice after various treatments after 21 day

Nanoceria (NCeO2) decorated flower-like MoS2 nanoflakes reported as a nanozyme for cancer photothermal therapy (PTT) [145]. Polyethylenimine (PEI) coated flower-like MoS2 nanoflakes surface decorated with cerium oxide NPs to formation of NCeO2-PEI-MoS2. The NCeO2 decoration considerably enhanced the photoconversion effectiveness (PCEs) of MoS2 nanoflakes. The different effects of NCeO2-PEI-MoS2 nanoflakes on cancer and normal cells were due to multi-enzyme mimics of NCeO2. Normal cells protect against oxidative damage via neutralization of free superoxide radicals and hydrogen peroxide by superoxide dismutase (SOD) and catalase enzyme mimic to decompose H2O2 into water and O2. Although, in acidic cancer cell NCeO2 work as a Fenton-like catalyst that dismutates H2O2 to OH·. Next, O2−· and H2O2 are formed by dismutating CO2 or ordinary molecular oxygen (O2). The formed.

ROS species (OH·, O2−· and H2O2) induce oxidative stress leading to cell death or apoptosis in cancer cells (Fig. 21).

Fig. 21

Schematic illustration of the use of NCeO2-PEI-MoS2 for selective enhanced photodynamic therapy

Sonodynamic therapy (SDT)

Ultrasound (US) can penetrate biological tissues, capable of activating sonosensitizers to generate toxic ROS molecules for cancer therapy modality named sonodynamic therapy (SDT). SDT can obviate the severe issue of low tissue-penetrating depth of traditional phototriggered therapies, but the SDT efficiency is still not satisfactory in battling cancer [146,147,148]. In SDT, ultrasound (US) can trigger sonosensitizers to produce ROS, bubbles, cavitation and hyperthermia. it has a good therapeutic effect on the treatment of deep malignant tumors. SDT is a selective method for treatment of deep malignant tumors, because US can precisely focus on the tumor region, target to activate sonosensitizers, and minimize the damage to the adjacent normal organs and tissues [146, 149]. The solid tumor microenvironment (TME) appears when there is critical hypoxia because of O2 consumption during SDT [150]. Thereby, enzyme mimic nanomaterials can also work as the synergistic agents to boost the therapy efficiency by alleviating tumor hypoxia. Nanoenzymes can convert the tumor-overexpressed hydrogen peroxide (H2O2) molecules into oxygen and enhancing the tumor oxygen level to boost SDT-induced ROS production. Liang et al. employed hollow Pt-CuS janus architecture for synergistic catalysis-enhanced sonodynamic and photothermal cancer therapy [151]. Sonosensitizer molecules (tetra-(4-aminophenyl) porphyrin, TAPP) loaded on inner cavities of hollow CuS to fulfillment SDT. Metallic Pt with enzyme like-activity catalyzed decomposition of endogenous overexpressed H2O2 to produce O2 and facilitates SDT efficacy (Fig. 22). Nanozymes can act as a carrier effectively deliver a sonosensitizer to the lesions and also provide a sonosensitizer with rich oxygen by their enzyme activities. It was found that the modification of a sonosensitizer onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze oxygen generation [152]. Such “blocking and activating” enzyme activity decreases the potential toxicity and side effects of nanozymes on normal tissues and helps realize controllable, active, and disease-loci-specific nanozyme activity behavior.

Fig. 22

Schematic illustration of the main synthesis procedures and antitumor mechanism of Pt-CuS NPs

Antibacterial applications

Infectious diseases caused by bacteria are the most growing global health problem, infecting millions of people every year [153]. Until now, a number of antibacterial materials, such as antibiotics, quaternary ammonium ion, metal ions, and biocides have been developed to counter the growth of dangerous bacteria [154, 155]. However, owing to high cost of the above materials, antibiotic resistance, and complex chemical processing, the provision of alternative antimicrobials is of particular importance [156]. It was found that artificial enzyme mimics are able to function as an antimicrobial against both Gram-positive and Gram-negative bacteria via increasing the transformation of H2O2 into ROS [157, 158]. Chen and coworkers have found that graphene quantum dot/silver nanoparticle (GQD/AgNP) hybrids with peroxidase and oxidase like functions demonstrate high antibacterial properties against both Gram-negative and Gram-positive bacteria via using oxygen instead of H2O2 [159]. The GQD/AgNP hybrids could induce release of ROS to oxidize the lipids in the cell membrane. After distribution of GQD/AgNP hybrids around the bacteria the surface morphology of the bacteria exhibited an evident conversion from a smooth cell membrane to a roughened and wrinkled appearance, denoting that the cell membrane had been destroyed and lost its original barrier action (Fig. 23I). The oxidization of the lipids in the cell membrane and disruption the cell metabolism result in bacteria death.

Fig. 23

I TEM images of E. coli cells (A), S. aureus cells (B), and drug resistant E.coli (C), before (A, B and C) and after (A-I, A-II, B-I, B-II, C-I and C-II) treatment with 20 μg/mL GQD-AgNP hybrids, II Cell viability of (a) E. coli and (b) S. aureus; the plate samples showing colonies of (c) E. coli and (d) S. aureus, III (a,b) The effect of the MSN-AuNPs based antibacterial system on the biofilm destruction of B. subtilis. (a) Pictures of crystal-violet-stained the remaining biofilms. (b) The remaining biofilms were quantified by crystal violet staining. (c,d) The effect of the MSN-AuNPs based antibacterial system on the biofilm formation of B. subtilis. (c) Pictures of crystal-violet-stained the generated biofilms. (d) Quantification of the generated biofilms by crystal violet staining, IV Schematic illustration of nanozyme-catalysed antibacterial performance of CuO NRs

Cai et al. also fabricated porous Pt/Ag nanoparticles with excellent multifunctional enzyme mimic activities to exert excellent antibacterial effects [160]. The multi-catalytic capability of Pt/Ag NPs as oxidase peroxidase and catalase, results in suppression of the bacteria growth (Fig. 23II).

Bacterial biofilms are determined as groups or clusters of bacteria, surrounded by a self-produced matrix of extracellular polymeric substances forming the three-dimensional structure. Bacterial biofilms are associated with health problems and diseases including chronic infections, biofouling of implants, as well as tooth decay and biomedical devices. Biofilms are difficult to destroy, because the biofilm mode of growth exerts the protection effect [161,162,163]. Tao et al. have also demonstrated intrinsic oxidase and peroxidase catalytic functions of bifunctionalized mesoporous silica-supported gold nanoparticles for biofilm destruction [164]. Treatment with both MSN-AuNPs and H2O2 led to breaking down the existing biofilm (Fig. 23III).

Light-absorbing characteristics of nanomaterials have created salient opportunities in applying light to activate nanomaterials for control of biological processes. In particular, combining the use of light as a trigger with the nanozyme activity of nanomaterials offers remarkable potential to control the antibacterial property [165, 166]. Karim’s group showed the ability of visible light to work as an external trigger for controlling the antibacterial property of semiconducting CuO nanorods (NRs) [167]. In visible light illumination, the apparent binding affinity of CuO NRs to H2O2 increased by over four times in comparation with non-illuminated conditions, (Fig. 23IV). The outcome of this distinct feature is progression in the rate of ROS production, so that, antibacterial efficiency of photoilluminated CuO NRs improved by elevating the OH· radical formation even at low H2O2 concentrations.

The surface morphology of nanocomposites has a key role in adjusting their catalytic functions. Thus the enzyme-like activity of metal-based nanomaterials could be controlled by modulating their exposed facets [168, 169]. Along these lines facet-dependent of palladium (Pd) nanocrystals have been demonstrated against Gram-positive and Gram-negative bacteria [170]. The antibacterial performance of Pd nanocrystals against Gram-positive bacteria is the consequence of the extent of their enzyme-like activity, that is {100}-faceted Pd cubes with higher activities destroy bacteria more effectively than {111}-faceted Pd octahedrons. This outcome has been corroborated with the dissociative energy profiles for the O2 molecule on the Pd {111} and {100} surfaces. The O2 binding on the Pd {111} facet has adsorption energy of − 0.85 eV, whereas for the O2 on the Pd {100} facet, the value is − 1.40 eV, indicating that the Pd {100} facet, present in the Pd cubes, exhibits a stronger affinity for the O2 molecule.

Water purification

Organic dyes are one of the widely used industrial products, which, their inseparable disposal poses serious risks to the environment [171]. Dyes generally cause water contamination and many problems to human health and environment, because they are toxic, mutagenic, carcinogenic and non-biodegradable. Therefore, the removal of dyes from wastewater is indispensable, particularly for securing aquatic life and mitigating the problem of water pollution [172, 173]. Among different removal technologies available for the removal of dye-containing wastewater, advanced oxidation processes (AOP) has been suggested as an excellent strategy [174, 175]. Fenton process as a one of the advanced oxidation technologies is a strong catalytic reaction used for environmental restoration. In Fenton chemistry, H2O2 is decomposed by soluble Fe2+ ions to produce highly oxidative species, i.e., hydroxyl radicals, according to the Haber–Weiss mechanism in Eq. (1) [176, 177]:

$${\text{Fe}}^{{{2} + }} + {\text{ H}}_{{2}} {\text{O}}_{{2}} \to {\text{Fe}}^{{{3} + }} + {\text{ HO}}^{ \cdot } + {\text{ OH}}^{ - }$$

The homogeneous Fenton process based on the aqueous mixture of ionic iron (Fe2+/Fe3+) and hydrogen peroxide (H2O2) suffers from sludge formation and pH limitations. Hence, much attempt has been devoted to the development of heterogeneous Fenton catalysts to address these issues [178, 179]. In that respect, iron oxide nanocomposite has attracted much interest for their applications in catalytic degradation of organic pollutants with H2O2 [180, 181]. Various forms of iron oxides such as Fe3O4, Fe2O3 and CuFe2O4 have been used as catalysts to activate H2O2 and generate ROS to remove of organic pollutants [182,183,184]. However, long reaction time and high concentration of H2O2 are the limitations of the H2O2-iron oxide catalytic system [185]. Therefore, the peroxidase-like activity of catalyst should be enhanced. Transition metal substituted magnetite could be introduced to improve the degradation of organic pollutants via Fenton reaction [186]. It was found that the degradation of methylene blue could be significantly improved through incorporation of niobium with magnetite catalyst. This ascribed to the generated oxygen vacancies on the surface of catalysts. Fe2+ cations were regenerated by introduction of Nb cations in Fenton oxidation cycle [187]. An ionothermal synthesis approach has been reported to generate Fe3O4 MNPs with unique intrinsic catalytic activity. In this synthesis strategy a deep eutectic solvent (DES) was applied for Fe2+/Fe3+ co-precipitation. As compared to Fe3O4 particles prepared in conventional commonly used solvents (water and ethyleneglycol), Fe3O4 MNPs made in DES possessed the higher activity for catalytic degradation of Rhodamine B (RhB) [188]. Utilization of some other Fenton catalyst was investigated for degradation of the organic dyes. Application of nanoceria, with excellent structural properties and high oxygen mobility, was studied for the removal of organic dyes. The proposed mechanism of Fenton-like reaction catalyzed by nanoceria is the activation of H2O2 by Ce4+/Ce3+ sites and then decompose into highly reactive hydroxyl radicals [189].

Summery and prospect

Since the discovery of Fe3O4 nanoparticles as peroxidase mimics in 2007, nanozymes as novel emerging and rapidly growing field have gained much attention. In this regard, metal and metal oxide nanomaterials are a good candidate to replace some complicated and expensive enzymes for using them as a novel and unique techniques in various areas such as bio nanotechnology and environmental governance. In comparison with natural enzyme, nanozymes encompasses many advantages including easy preparation, excellent stability, low cost, and good durability. In this review, we have summarized the recent achievements in application of metal and metal oxide-based nanozymes, including sensing, therapeutics, antibacterial application and water treatment. Obviously substantial progress has been achieved in research field of nanozyme; however, there are still numerous challenges remain to be addressed. First, the diversity of nanozymes is very low compared to natural enzymes; in other words, though many nanomaterials have been applied to mimic natural enzymes. Currently the redox enzyme mimics are still prevailing in the peroxidase-like nanozymes. Thus, new strategies are required to design and prepare other types of nanozymes. Second, in comparison with natural enzyme, nanozymes should provide a competitive catalytic selectivity and efficiency for practical applications. The surface modifications of nanomaterials by functional groups to make the active site for substrate recognition can boost the binding affinity and specificity of nanozymes. Furthermore, designing hybrid nanomaterials with synergetic effect can help to improve their activity. Third, in general, the developed nanozymes just have one enzymatic activity. The researchers need to pay more attention to construct nanozymes which catalyze cascade reactions to mimic the complex natural enzyme systems. Forth, although nanozymes offer cost-effective methods for application in various fields, noble metal nanomaterials (Au, Pt and Pd) don't take advantage of low cost. Therefore, the efforts should be propelled to synthesis and application of non-noble nanozymes as low cost and available materials. Fifth, potential toxicities of nanozymes should be carefully considered for biomedical applications. Sixth, the current research on applications of nanozymes are mainly limited to medicine and biotechnology. Future research should be focused on widening the practical applications of nanozymes in other fields including food, industry, agriculture or environment. The spread of the novel coronavirus disease (COVID19) has been a challenge that requires an emergent deployment of diagnostic and therapeutic options available. Development of a simple and sensitive immunodiagnostic method based on nanozymes can be useful for monitoring COVID19. Recently, a nanozyme chemiluminescence immunosensor for rapid and portable detection of SARS-CoV-2 spike antigen (S antigen) is developed [109]. The test paper platform based on a peroxidase nanozyme combines traditional enzymatic chemiluminescence analysis (CLIA) with lateral flow assay, which, facilitates early screening of SARS-CoV-2 infections. Furthermore, nanozymes possess the antiviral activity through catalyzing lipid peroxidation of the viral lipid envelope. Thus, nanozymes have the ability to prevent COVID19 transmission and infection.

Availability of data and materials

All data generated or analyzed during this study are included in the article.


  1. 1.

    Chen Y, Xianyu Y, Dong M, Zhang J, Zheng W, Qian Z, Jiang X. Cascade reaction-mediated assembly of magnetic/silver nanoparticles for amplified magnetic biosensing. Anal Chem. 2018;90(11):6906–12.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    Bornscheuer U, Huisman G, Kazlauskas RJ, Lutz S, Moore J, Robins K. Engineering the third wave of biocatalysis. Nature. 2012;485(7397):185.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  3. 3.

    Kavosi B, Salimi A, Hallaj R, Amani K. A highly sensitive prostate-specific antigen immunosensor based on gold nanoparticles/PAMAM dendrimer loaded on MWCNTS/chitosan/ionic liquid nanocomposite. Biosens Bioelectron. 2014;52:20–8.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  4. 4.

    Navaee A, Salimi A. Graphene-supported pyrene-functionalized amino-carbon nanotube: a novel hybrid architecture of laccase immobilization as effective bioelectrocatalyst for oxygen reduction reaction. J Mater Chem A. 2015;3(14):7623–30.

    CAS  Article  Google Scholar 

  5. 5.

    Singh A, Datta S, Sachdeva A, Maslanka S, Dykes J, Skinner G, Burr D, Whiting RC, Sharma SK. Evaluation of an enzyme-linked immunosorbent assay (ELISA) kit for the detection of botulinum neurotoxins A B, E, and F in selected food matrices. Health Security. 2015;13(1):37–44.

    PubMed  Article  PubMed Central  Google Scholar 

  6. 6.

    Tan DCL, Sato H. Enhancing catalytic activity of bioanode for glucose biofuel cell by compressing enzyme, mediator and carbon support through centrifugation. Chem A Eur J. 2017;23(48):11485–8.

    CAS  Article  Google Scholar 

  7. 7.

    Gao L, Yan X. Nanozymes: an emerging field bridging nanotechnology and biology. Sci China Life Sci. 2016;59(4):400–2.

    PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    Alizadeh N, Hallaj R, Salimi A. A highly sensitive electrochemical immunosensor for hepatitis B virus surface antigen detection based on Hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme-signal amplification. Biosens Bioelectron. 2017;94:184–92.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Ma C, Ma Y, Sun Y, Lu Y, Tian E, Lan J, Li J, Ye W, Zhang H. Colorimetric determination of Hg2+ in environmental water based on the Hg2+-stimulated peroxidase mimetic activity of MoS2-Au composites. J Colloid Interface Sci. 2019;537:554–61.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  10. 10.

    Jia H, Yang D, Han X, Cai J, Liu H, He W. Peroxidase-like activity of the Co3O4 nanoparticles used for biodetection and evaluation of antioxidant behavior. Nanoscale. 2016;8(11):5938–45.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    Hu X, Saran A, Hou S, Wen T, Ji Y, Liu W, Zhang H, He W, Yin J-J, Wu X. Au@ PtAg core/shell nanorods: tailoring enzyme-like activities via alloying. Rsc Adv. 2013;3(17):6095–105.

    CAS  Article  Google Scholar 

  12. 12.

    Wei H, Wang E. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. Chem Soc Rev. 2013;42(14):6060–93.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Alizadeh N, Salimi A, Sham T-K, Bazylewski P, Fanchini G. Intrinsic enzyme-like activities of cerium oxide nanocomposite and its application for extracellular H2O2 detection using an electrochemical microfluidic device. ACS Omega. 2020;12:5.

    Google Scholar 

  14. 14.

    Duan D, Fan K, Zhang D, Tan S, Liang M, Liu Y, Zhang J, Zhang P, Liu W, Qiu X. Nanozyme-strip for rapid local diagnosis of Ebola. Biosens Bioelectron. 2015;74:134–41.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  15. 15.

    Yan-Yan H, You-Hui L, Fang P, Jin-Song R, Xiao-Gang Q. The current progress of nanozymes in disease treatments. Prog Biochem Biophys. 2018;45(2):256–67.

    Google Scholar 

  16. 16.

    Farka ZK, Čunderlová V, Horáčková V, Pastucha MJ, Mikušová Z, Hlaváček AN, Skládal P. Prussian blue nanoparticles as a catalytic label in a sandwich nanozyme-linked immunosorbent assay. Analyt Chem. 2018;90:2348–54.

    CAS  Article  Google Scholar 

  17. 17.

    Yan T, Zhi-Yue Q, Zhuo-Bin X, Li-Zeng G. Antibacterial mechanism and applications of nanozymes. Prog Biochem Biophys. 2018;45(2):118–28.

    Google Scholar 

  18. 18.

    Wang X, Hu Y, Wei H. Nanozymes in bionanotechnology: from sensing to therapeutics and beyond. Inorg Chem Front. 2016;3(1):41–60.

    CAS  Article  Google Scholar 

  19. 19.

    Gao L, Zhuang J, Nie L, Zhang J, Zhang Y, Gu N, Wang T, Feng J, Yang D, Perrett S. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat Nanotechnol. 2007;2(9):577.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    Hu Y, Cheng H, Zhao X, Wu J, Muhammad F, Lin S, He J, Zhou L, Zhang C, Deng Y. Surface-enhanced Raman scattering active gold nanoparticles with enzyme-mimicking activities for measuring glucose and lactate in living tissues. ACS Nano. 2017;11(6):5558–66.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  21. 21.

    Wang Z, Yang X, Yang J, Jiang Y, He N. Peroxidase-like activity of mesoporous silica encapsulated Pt nanoparticle and its application in colorimetric immunoassay. Anal Chim Acta. 2015;862:53–63.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    Wang Q, Zhang L, Shang C, Zhang Z, Dong S. Triple-enzyme mimetic activity of nickel–palladium hollow nanoparticles and their application in colorimetric biosensing of glucose. Chem Commun. 2016;52(31):5410–3.

    CAS  Article  Google Scholar 

  23. 23.

    Zhang W, Dong J, Wu Y, Cao P, Song L, Ma M, Gu N, Zhang Y. Shape-dependent enzyme-like activity of Co3O4 nanoparticles and their conjugation with his-tagged EGFR single-domain antibody. Colloids Surf B. 2017;154:55–62.

    CAS  Article  Google Scholar 

  24. 24.

    Huang L, Zhang W, Chen K, Zhu W, Liu X, Wang R, Zhang X, Hu N, Suo Y, Wang J. Facet-selective response of trigger molecule to CeO2 1 1 0 for up-regulating oxidase-like activity. Chem Eng J. 2017;330:746–52.

    CAS  Article  Google Scholar 

  25. 25.

    Hu A-L, Deng H-H, Zheng X-Q, Wu Y-Y, Lin X-L, Liu A-L, Xia X-H, Peng H-P, Chen W, Hong G-L. Self-cascade reaction catalyzed by CuO nanoparticle-based dual-functional enzyme mimics. Biosens Bioelectron. 2017;97:21–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  26. 26.

    Han L, Shi J, Liu A. Novel biotemplated MnO2 1D nanozyme with controllable peroxidase-like activity and unique catalytic mechanism and its application for glucose sensing. Sensors Actuat B. 2017;252:919–26.

    CAS  Article  Google Scholar 

  27. 27.

    Ghosh S, Roy P, Karmodak N, Jemmis ED, Mugesh G. Nanoisozymes: crystal-facet-dependent enzyme-mimetic activity of V2O5 nanomaterials. Angew Chem. 2018;130(17):4600–5.

    Article  Google Scholar 

  28. 28.

    Li D, Liu B, Huang P-JJ, Zhang Z, Liu J. Highly active fluorogenic oxidase-mimicking NiO nanozymes. Chem Commun. 2018;54(88):12519–22.

    CAS  Article  Google Scholar 

  29. 29.

    Carpenter MA, Mathur S, Kolmakov A. Metal oxide nanomaterials for chemical sensors. Berlin: Springer; 2012.

    Google Scholar 

  30. 30.

    He Q, Liu J, Liu X, Li G, Chen D, Deng P, Liang J. Fabrication of amine-modified magnetite-electrochemically reduced graphene oxide nanocomposite modified glassy carbon electrode for sensitive dopamine determination. Nanomaterials. 2018;8(4):194.

    PubMed Central  Article  CAS  Google Scholar 

  31. 31.

    Tian Y, Deng P, Wu Y, Li J, Liu J, Li G, He Q. MnO2 nanowires-decorated reduced graphene oxide modified glassy carbon electrode for sensitive determination of bisphenol A. J Electrochem Soc. 2020;167(4):046514.

    CAS  Article  Google Scholar 

  32. 32.

    Tian Y, Deng P, Wu Y, Liu J, Li J, Li G, He Q. High sensitive voltammetric sensor for nanomolarity vanillin detection in food samples via manganese dioxide nanowires hybridized electrode. Microchem J. 2020;104:885.

    Google Scholar 

  33. 33.

    Huang Y, Liu Z, Liu C, Ju E, Zhang Y, Ren J, Qu X. Self-assembly of multi-nanozymes to mimic an intracellular antioxidant defense system. Angew Chem Int Ed. 2016;55(23):6646–50.

    CAS  Article  Google Scholar 

  34. 34.

    Alizadeh N, Salimi A, Hallaj R. Mimicking peroxidase-like activity of Co3O4-CeO2 nanosheets integrated paper-based analytical devices for detection of glucose with smartphone. Sens Actuat B. 2019;288:44–52.

    CAS  Article  Google Scholar 

  35. 35.

    Lee LA, Niu Z, Wang Q. Viruses and virus-like protein assemblies—Chemically programmable nanoscale building blocks. Nano Res. 2009;2(5):349–64.

    CAS  Article  Google Scholar 

  36. 36.

    Kwon KC, Ko HK, Lee J, Lee EJ, Kim K, Lee J. Enhanced in vivo tumor detection by active tumor cell targeting using multiple tumor receptor-binding peptides presented on genetically engineered human ferritin nanoparticles. Small. 2016;12(31):4241–53.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Jiang B, Yan L, Zhang J, Zhou M, Shi G, Tian X, Fan K, Hao C, Yan X. Biomineralization synthesis of the cobalt nanozyme in SP94-ferritin nanocages for prognostic diagnosis of hepatocellular carcinoma. ACS Appl Mater Interfaces. 2019;11(10):9747–55.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  38. 38.

    Lopez-Ruiz N, Curto VF, Erenas MM, Benito-Lopez F, Diamond D, Palma AJ, Capitan-Vallvey LF. Smartphone-based simultaneous pH and nitrite colorimetric determination for paper microfluidic devices. Anal Chem. 2014;86(19):9554–62.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  39. 39.

    Fu G, Sanjay ST, Li X. Cost-effective and sensitive colorimetric immunosensing using an iron oxide-to-Prussian blue nanoparticle conversion strategy. Analyst. 2016;141(12):3883–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Woo M-A, Kim M, Jung J, Park K, Seo T, Park H. A novel colorimetric immunoassay utilizing the peroxidase mimicking activity of magnetic nanoparticles. Int J Mol Sci. 2013;14(5):9999–10014.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  41. 41.

    Zhou Y, Huang X, Zhang W, Ji Y, Chen R, Xiong Y. Multi-branched gold nanoflower-embedded iron porphyrin for colorimetric immunosensor. Biosens Bioelectron. 2018;102:9–16.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  42. 42.

    Deng X, Fang Y, Lin S, Cheng Q, Liu Q, Zhang X. Porphyrin-based porous organic frameworks as a biomimetic catalyst for highly efficient colorimetric immunoassay. ACS Appl Mater Interfaces. 2017;9(4):3514–23.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Alizadeh N, Salimi A, Hallaj R. Mimicking peroxidase activity of Co2(OH)2CO3-CeO2 nanocomposite for smartphone based detection of tumor marker using paper-based microfluidic immunodevice. Talanta. 2018;189:100–10.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  44. 44.

    Jiao L, Zhang L, Du W, Li H, Yang D, Zhu C. Au@ Pt nanodendrites enhanced multimodal enzyme-linked immunosorbent assay. Nanoscale. 2019;11(18):8798–802.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  45. 45.

    Fu G, Sanjay ST, Zhou W, Brekken RA, Kirken RA, Li X. Exploration of nanoparticle-mediated photothermal effect of TMB-H2O2 colorimetric system and its application in a visual quantitative photothermal immunoassay. Anal Chem. 2018;90(9):5930–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Salimi A, Khezrian S, Hallaj R, Vaziry A. Highly sensitive electrochemical aptasensor for immunoglobulin E detection based on sandwich assay using enzyme-linked aptamer. Anal Biochem. 2014;466:89–97.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  47. 47.

    Shahdost-fard F, Salimi A, Khezrian S. Highly selective and sensitive adenosine aptasensor based on platinum nanoparticles as catalytical label for amplified detection of biorecognition events through H2O2 reduction. Biosens Bioelectron. 2014;53:355–62.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    Shahdost-fard F, Salimi A, Sharifi E, Korani A. Fabrication of a highly sensitive adenosine aptasensor based on covalent attachment of aptamer onto chitosan-carbon nanotubes-ionic liquid nanocomposite. Biosens Bioelectron. 2013;48:100–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  49. 49.

    Zhao R-N, Feng Z, Zhao Y-N, Jia L-P, Ma R-N, Zhang W, Shang L, Xue Q-W, Wang H-S. A sensitive electrochemical aptasensor for Mucin 1 detection based on catalytic hairpin assembly coupled with PtPdNPs peroxidase-like activity. Talanta. 2019;200:503–10.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  50. 50.

    Wang Y-W, Wang L, An F, Xu H, Yin Z, Tang S, Yang H-H, Song H. Graphitic carbon nitride supported platinum nanocomposites for rapid and sensitive colorimetric detection of mercury ions. Anal Chim Acta. 2017;980:72–8.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  51. 51.

    Cui W-R, Zhang C-R, Jiang W, Liang R-P, Wen S-H, Peng D, Qiu J-D. covalent organic framework nanosheet-based ultrasensitive and selective colorimetric sensor for trace Hg2+ detection. ACS Sust Chem Eng. 2019;15:9.

    Google Scholar 

  52. 52.

    Huang D, Niu C, Ruan M, Wang X, Zeng G, Deng C. Highly sensitive strategy for Hg2+ detection in environmental water samples using long lifetime fluorescence quantum dots and gold nanoparticles. Environ Sci Technol. 2013;47(9):4392–8.

    CAS  Article  Google Scholar 

  53. 53.

    Hizir MS, Top M, Balcioglu M, Rana M, Robertson NM, Shen F, Sheng J, Yigit MV. Multiplexed activity of perAuxidase: DNA-capped AuNPs act as adjustable peroxidase. Anal Chem. 2015;88(1):600–5.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  54. 54.

    Cheng H, Wu C, Liu J, Xu Z. Thiol-functionalized silica microspheres for online preconcentration and determination of mercury species in seawater by high performance liquid chromatography and inductively coupled plasma mass spectrometry. RSC Advances. 2015;5(25):19082–90.

    CAS  Article  Google Scholar 

  55. 55.

    Guo Y, Tao Y, Ma X, Jin J, Wen S, Ji W, Song W, Zhao B, Ozaki Y. A dual colorimetric and SERS detection of Hg2+ based on the stimulus of intrinsic oxidase-like catalytic activity of Ag-CoFe2O4/reduced graphene oxide nanocomposites. Chem Eng J. 2018;350:120–30.

    CAS  Article  Google Scholar 

  56. 56.

    Lian Q, Liu H, Zheng X, Li X, Zhang F, Gao J. Enhanced peroxidase-like activity of CuO/Pt nanoflowers for colorimetric and ultrasensitive Hg2+ detection in water sample. Appl Surf Sci. 2019;483:551–61.

    CAS  Article  Google Scholar 

  57. 57.

    Kong L, Yan L, Qu Z, Yan N, Li L. β-Cyclodextrin stabilized magnetic Fe3S4 nanoparticles for efficient removal of Pb (ii). Journal of Materials Chemistry A. 2015;3(30):15755–63.

    CAS  Article  Google Scholar 

  58. 58.

    Bian S, Shen C, Hua H, Zhou L, Zhu H, Xi F, Liu J, Dong X. One-pot synthesis of sulfur-doped graphene quantum dots as a novel fluorescent probe for highly selective and sensitive detection of lead (II). Rsc Advances. 2016;6(74):69977–83.

    CAS  Article  Google Scholar 

  59. 59.

    Huang K, Li B, Zhou F, Mei S, Zhou Y, Jing T. Selective solid-phase extraction of lead ions in water samples using three-dimensional ion-imprinted polymers. Anal Chem. 2016;88(13):6820–6.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  60. 60.

    Xu J, Zhang Y, Li L, Kong Q, Zhang L, Ge S, Yu J. Colorimetric and electrochemiluminescence dual-mode sensing of lead ion based on integrated lab-on-paper device. ACS Appl Mater Interfaces. 2018;10(4):3431–40.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    Liao H, Liu G, Liu Y, Li R, Fu W, Hu L. Aggregation-induced accelerating peroxidase-like activity of gold nanoclusters and their applications for colorimetric Pb2+ detection. Chem Commun. 2017;53(73):10160–3.

    CAS  Article  Google Scholar 

  62. 62.

    Kim MI, Ye Y, Won BY, Shin S, Lee J, Park HG. A highly efficient electrochemical biosensing platform by employing conductive nanocomposite entrapping magnetic nanoparticles and oxidase in mesoporous carbon foam. Adv Func Mater. 2011;21(15):2868–75.

    CAS  Article  Google Scholar 

  63. 63.

    Hur J, Park HG, Kim MI. Reagentless colorimetric biosensing platform based on nanoceria within an agarose gel matrix. Biosens Bioelectron. 2017;93:226–33.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  64. 64.

    Qu K, Shi P, Ren J, Qu X. Nanocomposite incorporating V2O5 nanowires and gold nanoparticles for mimicking an enzyme cascade reaction and its application in the detection of biomolecules. Chem A Eur J. 2014;20(24):7501–6.

    CAS  Article  Google Scholar 

  65. 65.

    He L, Lu Y, Gao X, Song P, Huang Z, Liu S, Liu Y. Self-cascade system based on cupric oxide nanoparticles as dual-functional enzyme mimics for ultrasensitive detection of silver ions. ACS Sust Chem Eng. 2018;6(9):12132–9.

    CAS  Article  Google Scholar 

  66. 66.

    Mao S, Chang J, Zhou G, Chen J. Nanomaterial-enabled rapid detection of water contaminants. Small. 2015;11(40):5336–59.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  67. 67.

    Amiri S, Navaee A, Salimi A, Ahmadi R. Zeptomolar detection of Hg2+ based on label-free electrochemical aptasensor: One step closer to the dream of single atom detection. Electrochem Commun. 2017;78:21–5.

    CAS  Article  Google Scholar 

  68. 68.

    Amiri S, Ahmadi R, Salimi A, Navaee A, Qaddare SH, Amini MK. Ultrasensitive and highly selective FRET aptasensor for Hg2+ measurement in fish samples using carbon dots/AuNPs as donor/acceptor platform. New J Chem. 2018;42(19):16027–35.

    CAS  Article  Google Scholar 

  69. 69.

    Chu KW, Chow KL. Synergistic toxicity of multiple heavy metals is revealed by a biological assay using a nematode and its transgenic derivative. Aquat Toxicol. 2002;61(1–2):53–64.

    Article  Google Scholar 

  70. 70.

    Peng C-F, Zhang Y-Y, Wang L-Y, Jin Z-Y, Shao G. Colorimetric assay for the simultaneous detection of Hg 2+ and Ag+ based on inhibiting the peroxidase-like activity of core–shell Au@ Pt nanoparticles. Anal Methods. 2017;9(30):4363–70.

    CAS  Article  Google Scholar 

  71. 71.

    Chen X, Zhai N, Snyder JH, Chen Q, Liu P, Jin L, Zheng Q, Lin F, Hu J, Zhou H. Colorimetric detection of Hg2+ and Pb2+ based on peroxidase-like activity of graphene oxide–gold nanohybrids. Anal Methods. 2015;7(5):1951–7.

    CAS  Article  Google Scholar 

  72. 72.

    Huang P-C, Shen M-Y, Yu H-H, Wei S-C, Luo S-C. Surface Engineering of phenylboronic acid-functionalized poly (3,4-ethylenedioxythiophene) for fast responsive and sensitive glucose monitoring. ACS Appl Bio Mater. 2018;1(1):160–7.

    CAS  Article  Google Scholar 

  73. 73.

    Zou W-S, Ye C-H, Wang Y-Q, Li W-H, Huang X-H. A hybrid ratiometric probe for glucose detection based on synchronous responses to fluorescence quenching and resonance light scattering enhancement of boronic acid functionalized carbon dots. Sens Actuat B. 2018;271:54–63.

    CAS  Article  Google Scholar 

  74. 74.

    Guo Y, Wang H, Ma X, Jin J, Ji W, Wang X, Song W, Zhao B, He C. Fabrication of Ag–Cu2O/reduced graphene oxide nanocomposites as surface-enhanced raman scattering substrates for in situ monitoring of peroxidase-like catalytic reaction and biosensing. ACS Appl Mater Interfaces. 2017;9(22):19074–81.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  75. 75.

    Lin Y, Yu P, Hao J, Wang Y, Ohsaka T, Mao L. Continuous and simultaneous electrochemical measurements of glucose, lactate, and ascorbate in rat brain following brain ischemia. Anal Chem. 2014;86(8):3895–901.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  76. 76.

    Feng L-L, Wu Y-X, Zhang D-L, Hu X-X, Zhang J, Wang P, Song Z-L, Zhang X-B, Tan W. Near infrared graphene quantum dots-based two-photon nanoprobe for direct bioimaging of endogenous ascorbic acid in living cells. Anal Chem. 2017;89(7):4077–84.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  77. 77.

    Ding Y, Zhao J, Li B, Zhao X, Wang C, Guo M, Lin Y. The CoOOH-TMB oxidative system for use in colorimetric and test strip based determination of ascorbic acid. Microchim Acta. 2018;185(2):131.

    Article  CAS  Google Scholar 

  78. 78.

    Zhu Y, Yang Z, Chi M, Li M, Wang C, Lu X. Synthesis of hierarchical Co3O4@ NiO core-shell nanotubes with a synergistic catalytic activity for peroxidase mimicking and colorimetric detection of dopamine. Talanta. 2018;181:431–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  79. 79.

    Xu H-H, Deng H-H, Lin X-Q, Wu Y-Y, Lin X-L, Peng H-P, Liu A-L, Xia X-H, Chen W. Colorimetric glutathione assay based on the peroxidase-like activity of a nanocomposite consisting of platinum nanoparticles and graphene oxide. Microchim Acta. 2017;184(10):3945–51.

    CAS  Article  Google Scholar 

  80. 80.

    Chi M, Chen S, Zhong M, Wang C, Lu X. Self-templated fabrication of FeMnO3 nanoparticle-filled polypyrrole nanotubes for peroxidase mimicking with a synergistic effect and their sensitive colorimetric detection of glutathione. Chem Commun. 2018;54(46):5827–30.

    CAS  Article  Google Scholar 

  81. 81.

    Yang Z, Ma F, Zhu Y, Chen S, Wang C, Lu X. A facile synthesis of CuFe2O4/Cu9S8/PPy ternary nanotubes as peroxidase mimics for the sensitive colorimetric detection of H2O2 and dopamine. Dalton Trans. 2017;46(34):11171–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  82. 82.

    Alizadeh N, Salimi A, Hallaj R, Fathi F, Soleimani F. Ni-hemin metal–organic framework with highly efficient peroxidase catalytic activity: toward colorimetric cancer cell detection and targeted therapeutics. J Nanobiotechnol. 2018;16(1):93.

    CAS  Article  Google Scholar 

  83. 83.

    Xie Y, Yin T, Wiegraebe W, He XC, Miller D, Stark D, Perko K, Alexander R, Schwartz J, Grindley JC. Detection of functional haematopoietic stem cell niche using real-time imaging. Nature. 2009;457(7225):97.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  84. 84.

    Shen Z, Wu A, Chen X. Current detection technologies for circulating tumor cells. Chem Soc Rev. 2017;46(8):2038–56.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  85. 85.

    Tian L, Qi J, Qian K, Oderinde O, Liu Q, Yao C, Song W, Wang Y. Copper (II) oxide nanozyme based electrochemical cytosensor for high sensitive detection of circulating tumor cells in breast cancer. J Electroanal Chem. 2018;812:1–9.

    CAS  Article  Google Scholar 

  86. 86.

    Tian L, Qi J, Qian K, Oderinde O, Cai Y, Yao C, Song W, Wang Y. An ultrasensitive electrochemical cytosensor based on the magnetic field assisted binanozymes synergistic catalysis of Fe3O4 nanozyme and reduced graphene oxide/molybdenum disulfide nanozyme. Sens Actuat B. 2018;260:676–84.

    CAS  Article  Google Scholar 

  87. 87.

    Zhang L-N, Deng H-H, Lin F-L, Xu X-W, Weng S-H, Liu A-L, Lin X-H, Xia X-H, Chen W. In situ growth of porous platinum nanoparticles on graphene oxide for colorimetric detection of cancer cells. Anal Chem. 2014;86(5):2711–8.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  88. 88.

    Tao Y, Lin Y, Huang Z, Ren J, Qu X. Incorporating graphene oxide and gold nanoclusters: a synergistic catalyst with surprisingly high peroxidase-like activity over a broad ph range and its application for cancer cell detection. Adv Mater. 2013;25(18):2594–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  89. 89.

    Maji SK, Mandal AK, Nguyen KT, Borah P, Zhao Y. Cancer cell detection and therapeutics using peroxidase-active nanohybrid of gold nanoparticle-loaded mesoporous silica-coated graphene. ACS Appl Mater Interfaces. 2015;7(18):9807–16.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  90. 90.

    Wang G-L, Xu X-F, Qiu L, Dong Y-M, Li Z-J, Zhang C. Dual responsive enzyme mimicking activity of AgX (X= Cl, Br, I) nanoparticles and its application for cancer cell detection. ACS Appl Mater Interfaces. 2014;6(9):6434–42.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  91. 91.

    Alizadeh N, Salimi A, Hallaj R, Fathi F, Soleimani F. CuO/WO3 nanoparticles decorated graphene oxide nanosheets with enhanced peroxidase-like activity for electrochemical cancer cell detection and targeted therapeutics. Mater Sci Eng, C. 2019;99:1374–83.

    CAS  Article  Google Scholar 

  92. 92.

    Mumtaz S, Wang L-S, Hussain SZ, Abdullah M, Huma Z, Iqbal Z, Creran B, Rotello VM, Hussain I. Dopamine coated Fe 3 O 4 nanoparticles as enzyme mimics for the sensitive detection of bacteria. Chem Commun. 2017;53(91):12306–8.

    CAS  Article  Google Scholar 

  93. 93.

    Kaittanis C, Santra S, Perez JM. Emerging nanotechnology-based strategies for the identification of microbial pathogenesis. Adv Drug Deliv Rev. 2010;62(4–5):408–23.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  94. 94.

    Das R, Dhiman A, Kapil A, Bansal V, Sharma TK. Aptamer-mediated colorimetric and electrochemical detection of Pseudomonas aeruginosa utilizing peroxidase-mimic activity of gold NanoZyme. Anal Bioanal Chem. 2019;411(6):1229–38.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  95. 95.

    Liu Y, Zhao C, Song X, Xu K, Wang J, Li J. Colorimetric immunoassay for rapid detection of Vibrio parahaemolyticus. Microchim Acta. 2017;184(12):4785–92.

    CAS  Article  Google Scholar 

  96. 96.

    Zhang L, Chen Y, Cheng N, Xu Y, Huang K, Luo Y, Wang P, Duan D, Xu W. Ultrasensitive detection of viable Enterobacter sakazakii by a continual cascade nanozyme biosensor. Anal Chem. 2017;89(19):10194–200.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  97. 97.

    Cheng N, Song Y, Zeinhom MM, Chang Y-C, Sheng L, Li H, Du D, Li L, Zhu M-J, Luo Y. Nanozyme-mediated dual immunoassay integrated with smartphone for use in simultaneous detection of pathogens. ACS Appl Mater Interfaces. 2017;9(46):40671–80.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  98. 98.

    D’Autréaux B, Toledano MB. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol. 2007;8(10):813–24.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  99. 99.

    Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discovery. 2009;8(7):579.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  100. 100.

    Zhang C, Bu W, Ni D, Zhang S, Li Q, Yao Z, Zhang J, Yao H, Wang Z, Shi J. Synthesis of iron nanometallic glasses and their application in cancer therapy by a localized Fenton reaction. Angew Chem Int Ed. 2016;55(6):2101–6.

    CAS  Article  Google Scholar 

  101. 101.

    Tang Z, Zhang H, Liu Y, Ni D, Zhang H, Zhang J, Yao Z, He M, Shi J, Bu W. Antiferromagnetic pyrite as the tumor microenvironment-mediated nanoplatform for self-enhanced tumor imaging and therapy. Adv Mater. 2017;29(47):1701683.

    Article  CAS  Google Scholar 

  102. 102.

    Deák M, Horváth GV, Davletova S, Török K, Sass L, Vass I, Barna B, Király Z, Dudits D. Plants ectopically expressing the ironbinding protein, ferritin, are tolerant to oxidative damage and pathogens. Nat Biotechnol. 1999;17(2):192.

    PubMed  Article  PubMed Central  Google Scholar 

  103. 103.

    Bai J, Jia X, Zhen W, Cheng W, Jiang X. A facile ion-doping strategy to regulate tumor microenvironments for enhanced multimodal tumor theranostics. J Am Chem Soc. 2017;140(1):106–9.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  104. 104.

    Yu L, Chen Y, Chen H. H2O2-responsive theranostic nanomedicine. Chin Chem Lett. 2017;28(9):1841–50.

    CAS  Article  Google Scholar 

  105. 105.

    Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Can Res. 1991;51(3):794–8.

    CAS  Google Scholar 

  106. 106.

    Peng F, Tu Y, van Hest JC, Wilson DA. Self-guided supramolecular cargo-loaded nanomotors with chemotactic behavior towards cells. Angew Chem Int Ed. 2015;54(40):11662–5.

    CAS  Article  Google Scholar 

  107. 107.

    Ranji-Burachaloo H, Gurr PA, Dunstan DE, Qiao GG. Cancer treatment through nanoparticle-facilitated fenton reaction. ACS Nano. 2018;12(12):11819–37.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  108. 108.

    Wang X, Zhong X, Liu Z, Cheng L. Recent progress of chemodynamic therapy-induced combination cancer therapy. Nano Today. 2020;35:100946.

    CAS  Article  Google Scholar 

  109. 109.

    Zhong Y, Li X, Chen J, Wang X, Wei L, Fang L, Kumar A, Zhuang S, Liu J. Recent advances in MOF-based nanoplatforms generating reactive species for chemodynamic therapy. Dalton Trans. 2020;49(32):11045–58.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  110. 110.

    Lin LS, Song J, Song L, Ke K, Liu Y, Zhou Z, Shen Z, Li J, Yang Z, Tang W. Simultaneous fenton-like ion delivery and glutathione depletion by MnO2-based nanoagent to enhance chemodynamic therapy. Angew Chem Int Ed. 2018;57(18):4902–6.

    CAS  Article  Google Scholar 

  111. 111.

    Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 2011;11(9):671.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  112. 112.

    Massagué J, Obenauf AC. Metastatic colonization by circulating tumour cells. Nature. 2016;529(7586):298.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  113. 113.

    Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009;15(3):232–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  114. 114.

    Zhao P, Tang Z, Chen X, He Z, He X, Zhang M, Liu Y, Ren D, Zhao K, Bu W. Ferrous-cysteine–phosphotungstate nanoagent with neutral pH fenton reaction activity for enhanced cancer chemodynamic therapy. Materials Horizons. 2019;6(2):369–74.

    CAS  Article  Google Scholar 

  115. 115.

    Ma P, Xiao H, Yu C, Liu J, Cheng Z, Song H, Zhang X, Li C, Wang J, Gu Z. Enhanced cisplatin chemotherapy by iron oxide nanocarrier-mediated generation of highly toxic reactive oxygen species. Nano letters. 2017;17(2):928–37.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  116. 116.

    Lin L, Huang T, Song J, Ou X-Y, Wang Z, Deng H, Tian R, Liu Y, Wang J-F, Liu Y. Synthesis of copper peroxide nanodots for H2O2 self-supplying chemodynamic therapy. J Am Chem Soc. 2019;15:23.

    Google Scholar 

  117. 117.

    Lin L-S, Cong Z-X, Li J, Ke K-M, Guo S-S, Yang H-H, Chen G-N. Graphitic-phase C3N4 nanosheets as efficient photosensitizers and pH-responsive drug nanocarriers for cancer imaging and therapy. J Mater Chem B. 2014;2(8):1031–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  118. 118.

    Lee K-T, Lu Y-J, Mi F-L, Burnouf T, Wei Y-T, Chiu S-C, Chuang E-Y, Lu S-Y. Catalase-modulated heterogeneous Fenton reaction for selective cancer cell eradication: SnFe2O4 nanocrystals as an effective reagent for treating lung cancer cells. ACS Appl Mater Interfaces. 2017;9(2):1273–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  119. 119.

    Dai Y, Yang Z, Cheng S, Wang Z, Zhang R, Zhu G, Wang Z, Yung BC, Tian R, Jacobson O. Toxic reactive oxygen species enhanced synergistic combination therapy by self-assembled metal-phenolic network nanoparticles. Adv Mater. 2018;30(8):1704877.

    Article  CAS  Google Scholar 

  120. 120.

    Wang J, Yi J. Cancer cell killing via ROS: to increase or decrease, that is the question. Cancer Biol Ther. 2008;7(12):1875–84.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  121. 121.

    Kim H-J, Lee J-H, Kim S-J, Oh GS, Moon H-D, Kwon K-B, Park C, Park BH, Lee H-K, Chung S-Y. Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity. J Neurosci. 2010;30(11):3933–46.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  122. 122.

    Sun K, Gao Z, Zhang Y, Wu H, You C, Wang S, An P, Sun C, Sun B. Enhanced highly toxic reactive oxygen species levels from iron oxide core–shell mesoporous silica nanocarrier-mediated Fenton reactions for cancer therapy. J Mater Chem B. 2018;6(37):5876–87.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  123. 123.

    Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, Hahn SM, Hamblin MR, Juzeniene A, Kessel D. Photodynamic therapy of cancer: an update. CA Cancer J Clin. 2011;61(4):250–81.

    PubMed  PubMed Central  Article  Google Scholar 

  124. 124.

    Huang P, Lin J, Wang X, Wang Z, Zhang C, He M, Wang K, Chen F, Li Z, Shen G. Light-triggered theranostics based on photosensitizer-conjugated carbon dots for simultaneous enhanced-fluorescence imaging and photodynamic therapy. Adv Mater. 2012;24(37):5104–10.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  125. 125.

    Zhang C, Qin W-J, Bai X-F, Zhang X-Z. Nanomaterials to relieve tumor hypoxia for enhanced photodynamic therapy. Nano Today. 2020;35:100960.

    CAS  Article  Google Scholar 

  126. 126.

    Dang J, He H, Chen D, Yin L. Manipulating tumor hypoxia toward enhanced photodynamic therapy (PDT). Biomater Sci. 2017;5(8):1500–11.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  127. 127.

    Li X, Kwon N, Guo T, Liu Z, Yoon J. Innovative strategies for hypoxic-tumor photodynamic therapy. Angew Chem Int Ed. 2018;57(36):11522–31.

    CAS  Article  Google Scholar 

  128. 128.

    De Simone G, Vitale RM, Di Fiore A, Pedone C, Scozzafava A, Montero J-L, Winum J-Y, Supuran CT. Carbonic anhydrase inhibitors: hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX. J Med Chem. 2006;49(18):5544–51.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  129. 129.

    Fan W, Bu W, Zhang Z, Shen B, Zhang H, He Q, Ni D, Cui Z, Zhao K, Bu J. Inside back cover: X-ray radiation-controlled NO-release for on-demand depth-independent hypoxic radiosensitization. Angewandte Chem Int. 2015;54(47):14191–14191.

    Article  Google Scholar 

  130. 130.

    Kim J, Cho HR, Jeon H, Kim D, Song C, Lee N, Choi SH, Hyeon T. Continuous O2-evolving MnFe2O4 nanoparticle-anchored mesoporous silica nanoparticles for efficient photodynamic therapy in hypoxic cancer. J Am Chem Soc. 2017;139(32):10992–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  131. 131.

    Li QF, Wang XR, Yang YW, Lin H. Hypoxia upregulates hypoxia inducible factor (HIF)-3α expression in lung epithelial cells: characterization and comparison with HIF-1α. Cell Res. 2006;16(6):548.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  132. 132.

    Zhang W, Li S, Liu X, Yang C, Hu N, Dou L, Zhao B, Zhang Q, Suo Y, Wang J. Oxygen-generating MnO2 nanodots-anchored versatile nanoplatform for combined chemo-photodynamic therapy in hypoxic cancer. Adv Func Mater. 2018;28(13):1706375.

    Article  CAS  Google Scholar 

  133. 133.

    Yang X, Yang Y, Gao F, Wei J-J, Qian C-G, Sun M-J. Biomimetic Hybrid Nanozymes with Self-Supplied H+ and Accelerated O2 Generation for Enhanced Starvation and Photodynamic Therapy against Hypoxic Tumors. Nano letters. 2019;5:9.

    Google Scholar 

  134. 134.

    Zhang Y, Wang F, Liu C, Wang Z, Kang L, Huang Y, Dong K, Ren J, Qu X. Nanozyme decorated metal–organic frameworks for enhanced photodynamic therapy. ACS Nano. 2018;12(1):651–61.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  135. 135.

    Singh N, Savanur MA, Srivastava S, D’Silva P, Mugesh G. A redox modulatory Mn3O4 nanozyme with multi-enzyme activity provides efficient cytoprotection to human cells in a Parkinson’s disease model. Angew Chem Int Ed. 2017;56(45):14267–71.

    CAS  Article  Google Scholar 

  136. 136.

    Hu X, Li F, Xia F, Guo X, Wang N, Liang L, Yang B, Fan K, Yan X, Ling D. Biodegradation-mediated enzymatic activity-tunable molybdenum oxide nanourchins for tumor-specific cascade catalytic therapy. J Am Chem Soc. 2019;8:65.

    Google Scholar 

  137. 137.

    Chen Q, Wen J, Li H, Xu Y, Liu F, Sun S. Recent advances in different modal imaging-guided photothermal therapy. Biomaterials. 2016;106:144–66.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  138. 138.

    Abdoon AS, Al-Ashkar EA, Kandil OM, Shaban AM, Khaled HM, El Sayed MA, El Shaer MM, Shaalan AH, Eisa WH, Eldin AAG. Efficacy and toxicity of plasmonic photothermal therapy (PPTT) using gold nanorods (GNRs) against mammary tumors in dogs and cats. Nanomed Nanotechnol Biol Med. 2016;12(8):2291–7.

    CAS  Article  Google Scholar 

  139. 139.

    Jung HS, Verwilst P, Sharma A, Shin J, Sessler JL, Kim JS. Organic molecule-based photothermal agents: an expanding photothermal therapy universe. Chem Soc Rev. 2018;47(7):2280–97.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  140. 140.

    Hu J-J, Cheng Y-J, Zhang X-Z. Recent advances in nanomaterials for enhanced photothermal therapy of tumors. Nanoscale. 2018;10(48):22657–72.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  141. 141.

    Zhi D, Yang T, Ohagan J, Zhang S, Donnelly RF. Photothermal therapy. J Controll Release. 2020;3:87.

    Google Scholar 

  142. 142.

    Park D, Ahn K-O, Jeong K-C, Choi Y. Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer. Nanotechnology. 2016;27(18):185102.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  143. 143.

    Xi J, Wang W, Da L, Zhang J, Fan L, Gao L. Au-PLGA hybrid nanoparticles with catalase-mimicking and near-infrared photothermal activities for photoacoustic imaging-guided cancer therapy. ACS Biomater Sci Eng. 2018;4(3):1083–91.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  144. 144.

    Fan L, Xu X, Zhu C, Han J, Gao L, Xi J, Guo R. Tumor catalytic-photothermal therapy with yolk-shell Gold@ carbon nanozymes. ACS Appl Mater Interfaces. 2018;10(5):4502–11.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  145. 145.

    Murugan C, Murugan N, Sundramoorthy AK, Anandhakumar S. Nanoceria decorated flower-like molybdenum sulphide nanoflakes: an efficient nanozyme to tumour selective ros generation and photo thermal therapy. Chem Commun. 2019;2:7.

    Article  CAS  Google Scholar 

  146. 146.

    Zhu P, Chen Y, Shi J. Nanoenzyme-augmented cancer sonodynamic therapy by catalytic tumor oxygenation. ACS Nano. 2018;12(4):3780–95.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  147. 147.

    Pan X, Bai L, Wang H, Wu Q, Wang H, Liu S, Xu B, Shi X, Liu H. Metal–organic-framework-derived carbon nanostructure augmented sonodynamic cancer therapy. Adv Mater. 2018;30(23):1800180.

    Article  CAS  Google Scholar 

  148. 148.

    Gao Z, Zheng J, Yang B, Wang Z, Fan H, Lv Y, Li H, Jia L, Cao W. Sonodynamic therapy inhibits angiogenesis and tumor growth in a xenograft mouse model. Cancer Lett. 2013;335(1):93–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  149. 149.

    Wang X, Zhong X, Gong F, Chao Y, Cheng L. Newly developed strategies for improving sonodynamic therapy. Materials Horizons. 2020;7(8):2028–46.

    CAS  Article  Google Scholar 

  150. 150.

    Zhang C, Zhao K, Bu W, Ni D, Liu Y, Feng J, Shi J. Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence. Angew Chem Int Ed. 2015;54(6):1770–4.

    CAS  Article  Google Scholar 

  151. 151.

    Liang S, Deng X, Chang Y, Sun C, Shao S, Xie Z, Xiao X, Ma P, Zhang H, Cheng Z. Intelligent hollow Pt-CuS janus architecture for synergistic catalysis-enhanced sonodynamic and photothermal cancer therapy. Nano letters. 2019;11:23.

    Article  CAS  Google Scholar 

  152. 152.

    Sun D, Pang X, Cheng Y, Ming J, Xiang S, Zhang C, Lv P, Chu C, Chen X, Liu G. Ultrasound-switchable nanozyme augments sonodynamic therapy against multidrug-resistant bacterial infection. ACS Nano. 2020;14(2):2063–76.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  153. 153.

    Choi K-H, Lee H-J, Park BJ, Wang K-K, Shin EP, Park J-C, Kim YK, Oh M-K, Kim Y-R. Photosensitizer and vancomycin-conjugated novel multifunctional magnetic particles as photoinactivation agents for selective killing of pathogenic bacteria. Chem Commun. 2012;48(38):4591–3.

    CAS  Article  Google Scholar 

  154. 154.

    Paladini F, Pollini M, Sannino A, Ambrosio L. Metal-based antibacterial substrates for biomedical applications. Biomacromol. 2015;16(7):1873–85.

    CAS  Article  Google Scholar 

  155. 155.

    Cocco AR, Rosa WL, Silva AF, Lund RG, Piva E. A systematic review about antibacterial monomers used in dental adhesive systems: Current status and further prospects. Dental Mater. 2015;31(11):1345–62.

    CAS  Article  Google Scholar 

  156. 156.

    Levy SB, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses. Nat Med. 2004;10(12s):S122.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  157. 157.

    Natalio F, André R, Hartog AF, Stoll B, Jochum KP, Wever R, Tremel W. Vanadium pentoxide nanoparticles mimic vanadium haloperoxidases and thwart biofilm formation. Nat Nanotechnol. 2012;7(8):530.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  158. 158.

    Gao L, Giglio KM, Nelson JL, Sondermann H, Travis AJ. Ferromagnetic nanoparticles with peroxidase-like activity enhance the cleavage of biological macromolecules for biofilm elimination. Nanoscale. 2014;6(5):2588–93.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  159. 159.

    Chen S, Quan Y, Yu Y-L, Wang J-H. Graphene quantum dot/silver nanoparticle hybrids with oxidase activities for antibacterial application. ACS Biomater Sci Eng. 2017;3(3):313–21.

    CAS  Article  Google Scholar 

  160. 160.

    Cai S, Jia X, Han Q, Yan X, Yang R, Wang C. Porous Pt/Ag nanoparticles with excellent multifunctional enzyme mimic activities and antibacterial effects. Nano Res. 2017;10(6):2056–69.

    CAS  Article  Google Scholar 

  161. 161.

    Swartjes JJ, Das T, Sharifi S, Subbiahdoss G, Sharma PK, Krom BP, Busscher HJ, van der Mei HC. A functional DNase I coating to prevent adhesion of bacteria and the formation of biofilm. Adv Func Mater. 2013;23(22):2843–9.

    CAS  Article  Google Scholar 

  162. 162.

    Hancock RE. A brief on bacterial biofilms. Nat Genet. 2001;29(4):360.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  163. 163.

    Wong GC, O’Toole GA. All together now: Integrating biofilm research across disciplines. MRS Bull. 2011;36(5):339–42.

    PubMed  PubMed Central  Article  Google Scholar 

  164. 164.

    Tao Y, Ju E, Ren J, Qu X. Bifunctionalized mesoporous silica-supported gold nanoparticles: intrinsic oxidase and peroxidase catalytic activities for antibacterial applications. Adv Mater. 2015;27(6):1097–104.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  165. 165.

    Velema WA, Van Der Berg JP, Hansen MJ, Szymanski W, Driessen AJ, Feringa BL. Optical control of antibacterial activity. Nat Chem. 2013;5(11):924.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  166. 166.

    Anderson SR, Mohammadtaheri M, Kumar D, O’Mullane AP, Field MR, Ramanathan R, Bansal V. Robust nanostructured silver and copper fabrics with localized surface plasmon resonance property for effective visible light induced reductive catalysis. Adv Mater Interf. 2016;3(6):1500632.

    Article  CAS  Google Scholar 

  167. 167.

    Karim MN, Singh M, Weerathunge P, Bian P, Zheng R, Dekiwadia C, Ahmed T, Walia S, Della Gaspera E, Singh S. Visible-light-triggered reactive-oxygen-species-mediated antibacterial activity of peroxidase-mimic CuO nanorods. ACS Appl Nano Mater. 2018;1(4):1694–704.

    CAS  Article  Google Scholar 

  168. 168.

    Gilroy KD, Ruditskiy A, Peng H-C, Qin D, Xia Y. Bimetallic nanocrystals: syntheses, properties, and applications. Chem Rev. 2016;116(18):10414–72.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  169. 169.

    Zhang Q, Zhou Y, Villarreal E, Lin Y, Zou S, Wang H. Faceted gold nanorods: nanocuboids, convex nanocuboids, and concave nanocuboids. Nano Lett. 2015;15(6):4161–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  170. 170.

    Fang G, Li W, Shen X, Perez-Aguilar JM, Chong Y, Gao X, Chai Z, Chen C, Ge C, Zhou R. Differential Pd-nanocrystal facets demonstrate distinct antibacterial activity against Gram-positive and Gram-negative bacteria. Nature communications. 2018;9(1):129.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  171. 171.

    Rasalingam S, Peng R, Koodali RT. An insight into the adsorption and photocatalytic degradation of rhodamine B in periodic mesoporous materials. Appl Catal B. 2015;174:49–59.

    Article  CAS  Google Scholar 

  172. 172.

    Soon AN, Hameed B. Degradation of Acid Blue 29 in visible light radiation using iron modified mesoporous silica as heterogeneous Photo-Fenton catalyst. Appl Catal A. 2013;450:96–105.

    CAS  Article  Google Scholar 

  173. 173.

    Zhang J, Li F, Sun Q. Rapid and selective adsorption of cationic dyes by a unique metal-organic framework with decorated pore surface. Appl Surf Sci. 2018;440:1219–26.

    CAS  Article  Google Scholar 

  174. 174.

    Gupta V, Khamparia S, Tyagi I, Jaspal D, Malviya A. Decolorization of mixture of dyes: a critical review. Global J Environ Sci Manag. 2015;1(1):71–94.

    CAS  Google Scholar 

  175. 175.

    Marçal L, De Faria E, Saltarelli M, Calefi P, Nassar E, Ciuffi K, Trujillano R, Vicente M, Korili S, Gil A. Amine-functionalized titanosilicates prepared by the sol−gel process as adsorbents of the azo-dye Orange II. Ind Eng Chem Res. 2010;50(1):239–46.

    Article  CAS  Google Scholar 

  176. 176.

    Haber F, Weiss J. Über die katalyse des hydroperoxydes. Naturwissenschaften. 1932;20(51):948–50.

    CAS  Article  Google Scholar 

  177. 177.

    Kehrer JP. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000;149(1):43–50.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  178. 178.

    Feng J, Hu X, Yue PL. Effect of initial solution pH on the degradation of Orange II using clay-based Fe nanocomposites as heterogeneous photo-Fenton catalyst. Water Res. 2006;40(4):641–6.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  179. 179.

    Bokare AD, Choi W. Review of iron-free Fenton-like systems for activating H2O2 in advanced oxidation processes. J Hazard Mater. 2014;275:121–35.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  180. 180.

    M. Pera-Titus, V. Garcı́a-Molina, M.A. Baños, J. Giménez, S. Esplugas, Degradation of chlorophenols by means of advanced oxidation processes: a general review, Applied Catalysis B: Environmental 47(4) (2004) 219–256.

  181. 181.

    Navalon S, Alvaro M, Garcia H. Heterogeneous Fenton catalysts based on clays, silicas and zeolites. Appl Catal B. 2010;99(1–2):1–26.

    CAS  Article  Google Scholar 

  182. 182.

    Nsabimana A, Kitte SA, Wu F, Qi L, Liu Z, Zafar MN, Luque R, Xu G. Multifunctional magnetic Fe3O4/nitrogen-doped porous carbon nanocomposites for removal of dyes and sensing applications. Appl Surf Sci. 2019;467:89–97.

    Article  CAS  Google Scholar 

  183. 183.

    Xiao C, Li J, Zhang G. Synthesis of stable burger-like α-Fe2O3 catalysts: formation mechanism and excellent photo-Fenton catalytic performance. J Clean Prod. 2018;180:550–9.

    CAS  Article  Google Scholar 

  184. 184.

    Yu D, Ni H, Wang L, Wu M, Yang X. Nanoscale-confined precursor of CuFe2O4 mediated by hyperbranched polyamide as an unusual heterogeneous Fenton catalyst for efficient dye degradation. J Clean Prod. 2018;186:146–54.

    CAS  Article  Google Scholar 

  185. 185.

    Wang M, Wang N, Tang H, Cao M, She Y, Zhu L. Surface modification of nano-Fe3O4 with EDTA and its use in H2O2 activation for removing organic pollutants. Catal Sci Technol. 2012;2(1):187–94.

    CAS  Article  Google Scholar 

  186. 186.

    Costa RC, Lelis M, Oliveira LC, Fabris JD, Ardisson JD, Rios RR, Silva CN, Lago RM. Remarkable effect of Co and Mn on the activity of Fe3−xMxO4 promoted oxidation of organic contaminants in aqueous medium with H2O2. Catal Commun. 2003;4(10):525–9.

    CAS  Article  Google Scholar 

  187. 187.

    Pouran SR, Aziz AA, Daud WMAW, Embong Z. Niobium substituted magnetite as a strong heterogeneous Fenton catalyst for wastewater treatment. Appl Surf Sci. 2015;351:175–87.

    Article  CAS  Google Scholar 

  188. 188.

    Chen F, Xie S, Huang X, Qiu X. Ionothermal synthesis of Fe3O4 magnetic nanoparticles as efficient heterogeneous Fenton-like catalysts for degradation of organic pollutants with H2O2. J Hazard Mater. 2017;322:152–62.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  189. 189.

    Hamoud HI, Finqueneisel G, Azambre B. Removal of binary dyes mixtures with opposite and similar charges by adsorption, coagulation/flocculation and catalytic oxidation in the presence of CeO2/H2O2 Fenton-like system. J Environ Manage. 2017;195:195–207.

    CAS  Article  Google Scholar 

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This work was supported by the Research Office of University of Kurdistan (Grant: 130645), and Iranian Nanotechnology Initiative (Grant: 116748).


This work is financially supported by the Research Office of University of Kurdistan (Grant Number 4.1261) and Iranian Nanotechnology initiative.

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NA wrote the paper with support from AS. All authors contributed to the general discussion. All authors read and approved the final manuscript.

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Correspondence to Abdollah Salimi.

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Alizadeh, N., Salimi, A. Multienzymes activity of metals and metal oxide nanomaterials: applications from biotechnology to medicine and environmental engineering. J Nanobiotechnol 19, 26 (2021).

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  • Nanozyme
  • Metal
  • Metal oxide
  • Sensing and biosensing
  • Cancer
  • Therapeutic
  • Diagnostics