Enzyme-like Catalytic Activity Research Articles

Recent Advances in Nanozyme Sensors Based on Metal–Organic Frameworks and Covalent–Organic Frameworks

Nanozymes are nanomaterials that exhibit enzyme-like catalytic activity, which have drawn increasing attention on account of their unique superiorities including very high robustness, low cost, and ease of modification. Metal–organic frameworks (MOFs) and covalent–organic frameworks (COFs) have emerged as promising candidates for nanozymes due to their abundant catalytic activity centers, inherent porosity, and tunable chemical functionalities. In this review, we first compare the enzyme-mimicking activity centers and catalytic mechanisms between MOF and COF nanozymes, and then summarize the recent research on designing and modifying MOF and COF nanozymes with inherent catalytic activity. Moreover, typical examples of sensing applications based on these nanozymes are presented, as well as the translation of enzyme catalytic activity into a visible signal response. At last, a discussion of current challenges is presented, followed by some future prospects to provide guidance for designing nanozyme sensors based on MOFs and COFs for practical applications.

MXene-based nanozymes remodel tumor microenvironment for heterojunction-enhanced sonodynamic and chemodynamic therapy to boost robust cancer immunotherapy

Reactive oxygen species (ROS)-mediated sonodynamic therapy (SDT) holds increasing potential in treating deep-seated tumor owing to the high tissue-penetration depth, but hardly controls remote metastasis. To trigger robust cancer immunotherapy against malignant metastatic cancers, we report the rational construction of Z-scheme heterojunctions through decorating biocompatible Co3O4 nanoparticles with multiple enzyme-like catalytic activities onto Ti3C2Tx nanosheets to realize the augmented SDT and chemodynamic therapy (CDT). The deposition of Co3O4 nanoparticles not only sensitizes the sonodynamic activity of Ti3C2Tx nanosheets owing to the regulation of separation dynamics of electron-hole pairs, but also achieves the cascade amplification of ROS generation through Co2+-mediated Fenton-like reaction, Co3+-facilitated GSH depletion, and catalytic decomposition of endogenous H2O2 to relieve hypoxia. More importantly, the immunosuppressive TME could be reversed by the greatly enhanced ROS levels, ultimately inducing immunogenic cell death that promotes robust systemic immune responses. The heterojunction-enhanced SDT and CDT via Co3O4@Ti3C2Tx could trigger robust cancer immunotherapy, which achieves the eradication of primary tumors and suppression of distant tumors. This work highlights the potential of heterojunction engineering-enhanced SDT and CDT to trigger robust cancer immunotherapy.

Single-atom nanozymes possessing robust multienzyme-mimetic catalytic properties for sensing of volatile alkaline gas

Volatile alkaline gases (VAGs) emitted from various sources, such as the food or chemical industry, pose potential harm to the natural environment and human health. Therefore, the development of a real-time, rapid, and cost-effective detection method is crucial. In this study, the enzyme-like catalytic types and activities of four different metal-based single-atom enzymes (Ga, Cu, Mn, and Zn SAzymes) were selected and evaluated. Among them, Ga SAzyme exhibited the most promising catalytic properties. Furthermore, the multienzyme catalytic properties of Ga SAzyme were utilized for the detection of ammonia, and it was found that its peroxidase-like (POD-like) activity showed a strong affinity for ammonia (Km = 0.05 mM). This detection strategy demonstrated high sensitivity, with a limit of detection (LOD) of 3.0 mM in the linear range of 0.01–0.05 M and 7.0 mM in the linear range of 0.075–0.25 M. Additionally, the method was characterized by fast response time (15 s) and low cost ($0.035 per sample). The proposed method holds great potential for the detection of VAGs from various sources in the future.

Atomic-scale strain engineering of atomically resolved Pt clusters transcending natural enzymes

Strain engineering plays an important role in tuning electronic structure and improving catalytic capability of biocatalyst, but it is still challenging to modify the atomic-scale strain for specific enzyme-like reactions. Here, we systematically design Pt single atom (Pt1), several Pt atoms (Ptn) and atomically-resolved Pt clusters (Ptc) on PdAu biocatalysts to investigate the correlation between atomic strain and enzyme-like catalytic activity by experimental technology and in-depth Density Functional Theory calculations. It is found that Ptc on PdAu (Ptc-PA) with reasonable atomic strain upshifts the d-band center and exposes high potential surface, indicating the sufficient active sites to achieve superior biocatalytic performances. Besides, the Pd shell and Au core serve as storage layers providing abundant energetic charge carriers. The Ptc-PA exhibits a prominent peroxidase (POD)-like activity with the catalytic efficiency (Kcat/Km) of 1.50 × 109 mM−1 min−1, about four orders of magnitude higher than natural horseradish peroxidase (HRP), while catalase (CAT)-like and superoxide dismutase (SOD)-like activities of Ptc-PA are also comparable to those of natural enzymes. Biological experiments demonstrate that the detection limit of the Ptc-PA-based catalytic detection system exceeds that of visual inspection by 132-fold in clinical cancer diagnosis. Besides, Ptc-PA can reduce multi-organ acute inflammatory damage and mitigate oxidative stress disorder.

Breaking Barriers in Photothermal Tumor Therapy: A Cascade of Strain-Engineered Nanozyme in Action.

Cancer, a deadly and constantly evolving disease, has always been difficult to treat due to the complexity of the tumor microenvironment (TME). Cancer nanomedicines are proving to be a much better alternative for treatment due to their stability and ability to provide an efficient targeted therapy. An amorphous alloy bimetallene with an introduction of 2 % tensile strain with photothermal multiple enzyme-like catalytic activity is being presented here that functions as a TME-responsive nanozyme. Labeled as RhRu, this bimetallene, under acidic conditions, functions as oxidase (OXD) - like, peroxidase (POD) - like and catalase (CAT) - like enzymes, by producing radicals and disrupting the tumor cells. This effect is enhanced especially upon irradiation of laser and introduction of tensile strain in its heterophase boundaries. This current highlight discusses the strain engineering tactic of la-RhRu bimetallene and its potency as an anti-tumor therapeutic.

H2S-Responsive NIR-II Fluorescent Nanozyme that Regulates Tumor Microenvironment for Activatable Synergistic CO Therapy/Catalytic Therapy/Immunotherapy.

Nanozyme catalytic therapy triggered by the tumor microenvironment (TME)-responsive enzyme-like catalytic activities is an emerging approach for tumor treatment. However, the poor catalytic efficiency of nanozymes in tumors and the toxic side effects on normal tissues limit their further development, primarily due to the limited uptake and penetration depth of nanozyme in tumor tissues. Here, a tumor-targeting TME and electric field stimuli-responsive nanozyme (AgPt@CaCO3-FA) is developed, which is capable of catalyzing the generation of ROS to induce cell death and releasing carbon monoxide (CO) specifically in tumor tissues for on-demand CO therapy and immunotherapy. Benefiting from the endogenous H2S activated NIR-II fluorescence (FL) imaging guidance, AgPt@CaCO3-FA can be delivered into the deeper site of tumor tissues resulted from the TME regulation via generated CO during the electrolysis process to improve the catalytic efficiency of nanozymes in tumors. Moreover, CO effectively relieve immunosuppression TME via reeducating tumor-supportive M2-like macrophages to tumoricidal M1-like macrophages and induce mitochondrial dysfunction by reducing mitochondrial membrane potential, triggering tumor cells apoptosis. The enzyme-like activities combined with CO therapy arouse distinct immunogenic cell death (ICD) effect. Therefore, AgPt@CaCO3-FA permits synergistic CO gas, catalytic therapy and immunotherapy, effectively eradicating orthotopic breast tumors and preventing tumor metastasis and recurrence.

NH2-MIL-88B@TP-TA@CuS for photothermal catalytic synergistic antibacterial activity

Reactive oxygen species (ROS) provide a promising way to fight bacterial infection and meet the persistent challenge of antibiotic resistance. Nanoenzyme mimics natural enzyme and becomes an effective regulator of ROS level. In this study, NH2-MIL-88B with high specific surface area was selected as the core, and the covalent organic skeleton material TP-TA COF was wrapped by "sequential growth" technology. Subsequently, through the second hydrothermal treatment, the inorganic material CuS with excellent photothermal performance was integrated into the outer layer, and the NH2-MIL-88B@TP-TA@CuSX composite nanoenzyme was synthesized. Different from the traditional nano-enzyme, NH2-MIL-88B@TP-TA@CuSX nano-enzyme still has good catalytic effect under neutral conditions (pH=7). In addition, NH2-MIL-88B@TP-TA@CuSX has good near infrared (NIR) absorption rate and high photothermal conversion efficiency (PTCE is 48.7 %), which can be used for photothermal treatment (PTT) of bacteria. Mild photothermal effect can further enhance the enzyme-like catalytic activity of NH2-MIL-88B@TP-TA@CuSX, so that H2O2 can be more efficiently catalyzed to produce a large number of ROS. The experimental results in vitro show that NH2-MIL-88B@TP-TA@CuSX can effectively kill Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in the presence of laser irradiation and H2O2.

A pH-responsive single-atom nanozyme for photothermal-augmented nanocatalytic tumor therapy

Based on the physiological conditions of the tumor microenvironment (TME), many effective therapeutic strategies have been reported by using nanocatalysts. The main challenge is the insufficient catalytic activity of nanocatalysts within the acidic TME, significantly constraining their therapeutic efficacy. Herein, a pH-responsive bifunctional platform is developed with multiple enzyme-like catalytic activities for synergistic tumor therapy by integrating Rh single atoms nanozymes (SA-Rh nanozymes) with photothermal therapy (PTT). The SA-Rh nanozymes display peroxidase-mimicking activities within tumor cells, inducing a synergistic effect of enhanced reactive oxygen species generation for collaborative cancer therapy involving both chemodynamic therapy and PTT. Additionally, SA-Rh nanozymes exhibit catalase mimicking activities, enabling the generation of oxygen, and facilitating efficient nanozyme catalytic therapy in a substrate-cycle manner. Moreover, the catalytic efficiency of SA-Rh nanozymes is found to be higher under weak acidic conditions (pH=6.0) compared to neutral conditions (pH=7.4), thereby enabling the maintenance of catalytic activity in an acidic environment. The incorporation of this feature enhances its catalytic activity within the TME, optimizing the efficacy of nanozyme. The remarkable near-infrared I region absorption capability confers SA-Rh nanozymes with exceptional PTT performance, achieving an impressive efficiency of 34.1 %. Therefore, the SA-Rh nanozymes exhibit a remarkable ability to induce apoptosis in cancer cells through synergistic CDT and PTT modalities, effectively overcoming the shortcomings of current nanozyme catalytic therapy.

Enhancing the Catalytic Activity of Laccase@Copper-Metal-Organic Framework Nanofractal Microspheres: Synergistic Contribution of the Mass Transfer and Electron Transfer Pathway.

Metal-organic frameworks (MOFs) are limited by small pores and buried active sites, and their enzyme-like catalytic activity is still very low. Herein, laccase was employed as the organic component to construct laccase@Cu3(BTC)2 nanofractal microspheres. During the preparation process, laccase adsorbed Cu2+ by electrostatic attractive interaction, then combined with Cu2+ by coordination interaction, and finally induced the in situ growth of H3BTC2 in multiple directions by electrostatic repulsion. Interestingly, electrostatic repulsion was tuned efficiently by adjusting the Cu2+ concentration to obtain laccase@Cu3(BTC)2 nanofractal microspheres (nanosheet microspheres, nanorod microspheres, and nanoneedle microspheres). Laccase@Cu3(BTC)2 nanorod microspheres exhibited the highest catalytic efficiency, which was 14-fold higher than that of smooth microspheres. The mechanism of the improvement of catalytic activity in the degradation of BPA was proposed for the first time. The enhanced catalytic activity depended on the adsorption effect of the nanorod framework and dual cycle synergistic catalysis of Cu+/Cu2+ active sites, which accelerated substrate diffusion and electron transfer. The catalytic mechanism of enzyme@MOF nanofractal microspheres not only deepens our understanding of enzyme and MOF synergistic catalysis but also provides new insights into the design of catalysts.

NIR-II Light-Driven Genetically Engineered Exosome Nanocatalysts for Efficient Phototherapy against Glioblastoma.

Glioblastoma (GBM) poses a significant therapeutic challenge due to its invasive nature and limited drug penetration through the blood-brain barrier (BBB). In response, here we present an innovative biomimetic approach involving the development of genetically engineered exosome nanocatalysts (Mn@Bi2Se3@RGE-Exos) for efficient GBM therapy via improving the BBB penetration and enzyme-like catalytic activities. Interestingly, a photothermally activatable multiple enzyme-like reactivity is observed in such a nanosystem. Upon NIR-II light irradiation, Mn@Bi2Se3@RGE-Exos are capable of converting hydrogen peroxide into hydroxyl radicals, oxygen, and superoxide radicals, providing a peroxidase (POD), oxidase (OXD), and catalase (CAT)-like nanocatalytic cascade. This consequently leads to strong oxidative stresses to damage GBM cells. In vitro, in vivo, and proteomic analysis further reveal the potential of Mn@Bi2Se3@RGE-Exos for the disruption of cellular homeostasis, enhancement of immunological response, and the induction of cancer cell ferroptosis, showcasing a great promise in anticancer efficacy against GBM with a favorable biosafety profile. Overall, the success of this study provides a feasible strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM.

Transition-metal-based nanozymes for biosensing and catalytic tumor therapy.

Nanozymes, as an emerging class of enzyme mimics, have attracted much attention due to their adjustable catalytic activity, low cost, easy modification, and good stability. Researchers have made great efforts in developing and applying high-performance nanozymes. Recently, transition-metal-based nanozymes have been designed and widely developed because they possess unique photoelectric properties and high enzyme-like catalytic activities. To highlight these achievements and help researchers to understand the research status of transition-metal-based nanozymes, the development of transition-metal-based nanozymes from material characteristics to biological applications is summarized. Herein, we focus on introducing six categories of transition-metal-based nanozymes and highlight their progress in biomarker sensing and catalytic therapy for tumors. We hope that this review can guide the further development of transition-metal-based nanozymes and promote their practical applications in cancer diagnosis and treatment.

Nanozymes for Treating Ocular Diseases.

Nanozymes, characterized by their nanoscale size and enzyme-like catalytic activities, exhibit diverse therapeutic potentials, including anti-oxidative, anti-inflammatory, anti-microbial, and anti-angiogenic effects. These properties make them highly valuable in nanomedicine, particularly ocular therapy, bypassing the need for systemic delivery. Nanozymes show significant promise in tackling multi-factored ocular diseases, particularly those influenced by oxidation and inflammation, like dry eye disease, and age-related macular degeneration. Their small size, coupled with their ease of modification and integration into soft materials, facilitates the effective penetration of ocular barriers, thereby enabling targeted or prolonged therapy within the eye. This review is dedicated to exploring ocular diseases that are intricately linked to oxidation and inflammation, shedding light on the role of nanozymes in managing these conditions. Additionally, recent studies elucidating advanced applications of nanozymes in ocular therapeutics, along with their integration with soft materials for disease management, are discussed. Finally, this review outlines directions for future investigations aimed at bridging the gap between nanozyme research and clinical applications.

Dual-functionalized aramid fiber as an efficient heterogeneous acid-base bifunctional catalyst for the one-pot tandem reaction

Acid-base bifunctional catalysis represents a significant approach for achieving enzyme-like catalytic activity. In this study, we present a concise and direct approach for constructing acid-base bifunctional aramid fiber catalysts, enabling one-pot tandem deacetalization-Knoevenagel reactions in an aqueous environment. The fiber catalysts were conveniently prepared from commercially available aramid fiber using a straightforward two-step procedure, and comprehensively characterized using various detection techniques. Additionally, the acid-base cooperativity of the AF catalyst was effectively controlled through the manipulation of the acid-base ratios within the catalysts. Notably, the AF-SN1/2 catalyst exhibited superior catalytic activity in the one-pot tandem deprotection-Knoevenagel reaction at room temperature, resulting in the production of high yields. Moreover, the AF-SN1/2 catalyst demonstrated exceptional recyclability and performed admirably in a scaled-up experiment utilizing a straightforward fixed-bed reactor. These findings suggest that the AF-SN1/2 catalyst holds significant promise for future applications in cleaner industrial processes.

"Two-in-One" PtPdCu Trimetallic Multifunctional Nanoparticles-Mediated Dual-Signal-Integrated Aptasensor for Ultradetection of Enrofloxacin.

Balancing the accuracy and simplicity of aptasensors is a challenge in their construction. This study addresses this issue by leveraging the remarkable loading capacity and peroxidase-like catalytic activity of PtPdCu trimetallic nanoparticles, which reduces the reliance on precious metals. A dual-signal readout aptasensor for enrofloxacin (ENR) detection is designed, incorporating DNA dynamic network cascade reactions to further amplify the output signal. Exploiting the strong loading capacity of PtPdCu nanoparticles, they are self-assembled with thionine (Thi) to form a signal label capable of generating signals in two independent modes. The label exhibits excellent enzyme-like catalytic activity and enhances electron transfer capabilities. Differential pulse voltammetry (DPV) and square-wave voltammetry (SWV) are employed to independently read signals from the oxidation-reduction reaction of Thi and the catalytic oxidation of hydroquinone (HQ) to benzoquinone (BQ) by H2O2. The introduced DNA dynamic network cascade reaction modularizes sample processing and electrode surface signal generation, avoiding electrode contamination and efficiently increasing the output of the catalyzed hairpin assembly (CHA) cycle. Under optimized conditions, the developed aptasensor demonstrates detection limits of 0.112 (DPV mode) and 0.0203 pg/mL (SWV mode). Additionally, the sensor successfully detected enrofloxacin in real samples, expanding avenues for designing dual-mode signal amplification strategies.

A Multifunctional Nanozyme Integrating Antioxidant, Antimicrobial and Pro-Vascularity for Skin Wound Management.

Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bacterial infection during the wound healing process. There is still great potential for nanozymes to increase their therapeutic functional diversity and efficacy. Herein, copper-doped hollow mesopores cerium oxide (Cu-HMCe) nanozymes with multifunctional of antioxidant, antimicrobial and pro-vascularity is successfully prepared. Cu-HMCe can be efficiently prepared through a simple and rapid solution method and displays sound physiological stability. The biocompatibility, pro-angiogenic, antimicrobial, and antioxidant properties of Cu-HMCe were assessed. Moreover, a full-thickness skin defect infection model was utilized to investigate the wound healing capacity, as well as anti-inflammatory and pro-angiogenic properties of nanozymes in vivo. Both in vitro and in vivo experiments have substantiated Cu-HMCe's remarkable biocompatibility. Moreover, Cu-HMCe possesses potent antioxidant enzyme-like catalytic activity, effectively clearing DPPH radicals (with a scavenging rate of 80%), hydroxyl radicals, and reactive oxygen species. Additionally, Cu-HMCe exhibits excellent antimicrobial and pro-angiogenic properties, with over 70% inhibition of both E. coli and S. aureus. These properties collectively promote wound healing, and the wound treated with Cu-HMCe achieved a closure rate of over 90% on the 14th day. The results indicate that multifunctional Cu-HMCe with antioxidant, antimicrobial, and pro-angiogenic properties was successfully prepared and exhibited remarkable efficacy in promoting wound healing. This nanozymes providing a promising strategy for skin repair.

Precise Tuning of the D-Band Center of Dual-Atomic Enzymes for Catalytic Therapy.

Single-atom nanozyme-based catalytic therapy is of great interest in the field of tumor catalytic therapy; however, their development suffers from the low affinity of nanozymes to the substrates (H2O2 or O2), leading to deficient catalytic activity in the tumor microenvironment. Herein, we report a new strategy for precisely tuning the d-band center of dual-atomic sites to enhance the affinity of metal atomic sites and substrates on a class of edge-rich N-doped porous carbon dual-atomic sites Fe-Mn (Fe1Mn1-NCe) for greatly boosting multiple-enzyme-like catalytic activities. The as-made Fe1Mn1-NCe achieved a much higher catalytic efficiency (Kcat/Km = 4.01 × 105 S-1·M-1) than Fe1-NCe (Kcat/Km = 2.41 × 104 S-1·M-1) with an outstanding stability of over 90% activity retention after 1 year, which is the best among the reported dual-atom nanozymes. Theoretical calculations reveal that the synergetic effect of Mn upshifts the d-band center of Fe from -1.113 to -0.564 eV and enhances the adsorption capacity for the substrate, thus accelerating the dissociation of H2O2 and weakening the O-O bond on O2. We further demonstrated that the superior enzyme-like catalytic activity of Fe1Mn1-NCe combined with photothermal therapy could effectively inhibit tumor growth in vivo, with an inhibition rate of up to 95.74%, which is the highest value among the dual-atom artificial enzyme therapies reported so far.

Atomic Engineering of Single-Atom Nanozymes for Biomedical Applications.

Single-atom nanozymes (SAzymes) showcase not only uniformly dispersed active sites but also meticulously engineered coordination structures. These intricate architectures bestow upon them an exceptional catalytic prowess, thereby captivating numerous minds and heralding a new era of possibilities in the biomedical landscape. Tuning the microstructure of SAzymes on the atomic scale is a key factor in designing targeted SAzymes with desirable functions. This review first discusses and summarizes three strategies for designing SAzymes and their impact on reactivity in biocatalysis. The effects of choices of carrier, different synthesis methods, coordination modulation of first/second shell, and the type and number of metal active centers on the enzyme-like catalytic activity are unraveled. Next, a first attempt is made to summarize the biological applications of SAzymes in tumor therapy, biosensing, antimicrobial, anti-inflammatory, and other biological applications from different mechanisms. Finally, how SAzymes are designed and regulated for further realization of diverse biological applications is reviewed and prospected. It is envisaged that the comprehensive review presented within this exegesis will furnish novel perspectives and profound revelations regarding the biomedical applications of SAzymes.

Multicolor Biosensor of Hyaluronidase by the Regulation of Enzyme-Like Catalytic Activity of Au Nanoclusters through Changes in the Aggregation State

Multicolor Biosensor of Hyaluronidase by the Regulation of Enzyme-Like Catalytic Activity of Au Nanoclusters through Changes in the Aggregation State

Poly-β-cyclodextrin strengthen Pr6O11 porous oxidase mimic for dual-channel visual recognition of bioactive cysteine and Fe2.

To conveniently monitor bioactive cysteine (Cys) and Fe2+ in practice, a kind of poly-β-cyclodextrin strengthen praseodymium oxide (Pr6O11) porous oxidase mimic (p-β-CD@Pr6O11) was constructed by virtue of the strong coordination between nano Pr6O11 and poly-β-cyclodextrin substrate. After its microstructure and physicochemical property were characterized in detail, it was noted that porous p-β-CD@Pr6O11 exhibited excellent enzyme-like catalytic activity to accelerate the oxidation of 3,3',5,5,'-tetramethylbanzidine (TMB) and 2,2'-azinobis (3-ethylbenzo-thiazoline-6-sulfonic acid) ammonium salt (ABTS) with significant color-enhancement effect in the air. Based on the signal amplification, trace Cys could exclusively deteriorate the UV-vis absorbance at 653 nm of p-β-CD@Pr6O11-TMB and Fe2+ alter the one at 729 nm of p-β-CD@Pr6O11-ABTS with visual color changes. Under the optimized conditions, the proposed p-β-CD@Pr6O11-TMB and p-β-CD@Pr6O11-ABTS systems were successfully applied for dual-channel monitoring of Cys in Cys capsules and fetal bovine serum and Fe2+ in agricultural products with quite low detection limits, i.e., 7.8×10-9 mol·L-1 for Cys and 6.93×10-8 mol·L-1 (S/N=3) for Fe2+, respectively. The synergetic-enhancement detection mechanisms to Cys and Fe2+ were also proposed.

Co, Fe Dual-Doped MoS2 Nanosheets on Polypyrrole Microtubes as Effective Peroxidase Mimics for Glutathione Sensing.

Heteroatom doping is considered an effective way to enhance the catalytic activity of MoS2 nanosheets (NSs). In the paper, dual-metal doping was proposed to incorporate Fe and Co into hierarchical MoS2 ultrathin NSs, which grew directly on polypyrrole microtubes (Fe, Co-MoS2@PPy), for the enhanced enzyme-like catalytic reaction. The particular hollow tubular structure realized effective electron transfer. The doped Fe and Co tuned the electronic architecture of the MoS2 NSs to enhance the enzyme-like catalytic activity. The abundant exposed void spaces facilitated ion diffusion/penetration between the PPy interlayer and Fe-Co doped MoS2 shell, leading to heterostructured synergistic effects. Therefore, the synthesized Fe and Co-MoS2@PPy composites showed remarkable catalytic activity. The high catalytic efficiency of Fe and Co-MoS2@PPy was confirmed with the reaction of tetramethylbenzidine (TMB) and H2O2 for visible detection. The blue color disappeared after adding glutathione (GSH). Thus, this procedure was used as a convenient way to detect GSH with a detection limit of 0.76 μM. The dual-metal-doped strategy was confirmed to improve the performance of MoS2 nanocomposites and could be used as a promising matrix for other applications, such as electrochemical energy conversion, medical diagnosis, and others.