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Diabetic foot ulcers (DFU) are chronic, refractory wounds caused by diabetic neuropathy, vascular disease, and bacterial infection, and have become one of the most serious and persistent complications of diabetes mellitus because of their high incidence and difficulty in healing. Its malignancy results from a complex microenvironment that includes a series of unfriendly physiological states secondary to hyperglycemia, such as recurrent infections, excessive oxidative stress, persistent inflammation, and ischemia and hypoxia. However, current common clinical treatments, such as antibiotic therapy, insulin therapy, surgical debridement, and conventional wound dressings all have drawbacks, and suboptimal outcomes exacerbate the financial and physical burdens of diabetic patients. Therefore, development of new, effective and affordable treatments for DFU represents a top priority to improve the quality of life of diabetic patients. In recent years, nanozymes-based diabetic wound therapy systems have been attracting extensive interest by integrating the unique advantages of nanomaterials and natural enzymes. Compared with natural enzymes, nanozymes possess more stable catalytic activity, lower production cost and greater maneuverability. Remarkably, many nanozymes possess multienzyme activities that can cascade multiple enzyme-catalyzed reactions simultaneously throughout the recovery process of DFU. Additionally, their favorable photothermal-acoustic properties can be exploited for further enhancement of the therapeutic effects. In this review we first describe the characteristic pathological microenvironment of DFU, then discuss the therapeutic mechanisms and applications of nanozymes in DFU healing, and finally, highlight the challenges and perspectives of nanozyme development for DFU treatment.

Nanozymes have obvious advantages in improving the efficiency of cancer treatment. However, due to the lack of tissue specificity, low catalytic efficiency, and so on, their clinical applications are limited. Herein, the nanoplatform CeO2@ICG@GOx@HA (CIGH) with self‐accelerated cascade reactions is constructed. The as‐prepared nanozyme shows the superior oxidase (OXD)‐like, superoxide dismutase (SOD)‐like, catalase (CAT)‐like and peroxidase (POD)‐like activities. At the same time, under 808 nm near‐infrared (NIR) irradiation, the photodynamic and photothermal capabilities are also significantly enhanced due to the presence of indocyanine green (ICG). We demonstrate that the nanozyme CIGH can efficiently accumulate in the tumor and exhibit amplified cascade antitumor effects with negligible systemic toxicity through the combination of photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT) and starvation therapy. The nanozyme prepared in this study provides a promising candidate for catalytic nanomedicines for efficient tumor therapy. [ABSTRACT FROM AUTHOR]

Preserving pulp viability and promoting pulp regeneration in pulpitis have attracted widespread attention. Restricted by the oxidative stress microenvironment of dental pulpitis, excessive reactive oxygen and nitrogen species (RONS) trigger uncontrolled inflammation and exacerbate pulp tissue destruction. However, modulating redox homeostasis in inflamed pulp tissue to promote pulp regeneration remains a great challenge. Herein, this work proposes an effective antioxidative system (C-NZ/GelMA) consisting of carbon dot nanozymes (C-NZ) with gelatin methacryloyl (GelMA) to modulate the pulpitis microenvironment for dental pulp regeneration by utilizing the antioxidant properties of C-NZ and the mechanical support of an injectable GelMA hydrogel. This system effectively scavenges RONS to normalize intracellular redox homeostasis, relieving oxidative stress damage. Impressively, it can dramatically enhance the polarization of regenerative M2 macrophages. This study revealed that the C-NZ/GelMA hydrogel promoted pulp regeneration and dentin repair through its outstanding antioxidant, antiapoptotic, and anti-inflammatory effects, suggesting that the C-NZ/GelMA hydrogel is highly valuable for pulpitis treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Histamine may lead to low blood pressure, skin flushing and edema when it accumulates in large amounts in the body. Therefore, establishing sensitive methods for the detection of histamine in foods is extremely important to ensure food safety and human health.The MI‐Cu‐GMP NPs (2‐methylimidazole‐copper‐guanosine monophosphate nanozymes) with high laccase‐like activity were synthesized. Using the prepared molecular imprinted membrane as biomimetic antibody and MI‐Cu‐GMP NPs as marker, a sensitive direct competitive biomimetic enzyme‐linked immunoassay (BELISA) method for rapid detection of the histamine in foods was developed. Under optimal conditions, the limit of detection (LOD, IC15) and sensitivity (IC50) of the BELISA method for histamine was 0.05 mg L−1 and 1.22 mg L−1, respectively. The liquor samples spiked with histamine was detected by the BELISA method with satisfactory recoveries ranging from 90.00% to 116.00%. Further, the level of histamine in three samples (cooking wine, rice vinegar and soy sauce) was tested by the BELISA and high‐performance liquid chromatography (HPLC), with no significant difference found between the two methods.Given the advantages, the established BELISA method is expected to provide practical guidance for the monitoring of histamine in food and provides a foundation for the detection of other food hazards. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) regulation for single‐atom nanozymes (SAzymes), e.g. Fe−N−C, is a key scientific issue that determines the activity, selectivity, and stability of aerobic reaction. However, the poor understanding of ROS formation mechanism on SAzymes greatly hampers their wider deployment. Herein, inspired by cytochromes P450 affording bound ROS intermediates in O2 activation, we report Fe−N−C containing the same FeN4 but with tunable second‐shell coordination can effectively regulate ROS production pathways. Remarkably, compared to the control Fe−N−C sample, the second‐shell sulfur functionalized Fe−N−C delivered a 2.4‐fold increase of oxidase‐like activity via the bound Fe=O intermediate. Conversely, free ROS (⋅O2−) release was significantly reduced after functionalization, down to only 17 % of that observed for Fe−N−C. The detailed characterizations and theoretical calculations revealed that the second‐shell sulfur functionalization significantly altered the electronic structure of FeN4 sites, leading to an increase of electron density at Fermi level. It enhanced the electron transfer from active sites to the key intermediate *OOH, thereby ultimately determining the type of ROS in aerobic oxidation process. The proposed Fe−N−Cs with different second‐shell anion were further applied to three aerobic oxidation reactions with enhanced activity, selectivity, and stability. [ABSTRACT FROM AUTHOR]

Electrogenerated hydrophilic carbon (EHC) nanomaterials emerge as a highly attractive option for mimicking the activity of the superoxide dismutase enzyme (SOD) due to their exceptional water solubility and electron-transfer reversibility. Motivated by these properties, the EHC nanomaterials were utilized to assess the effect of ionic strength on the SOD-like activity. Superoxide anion radicals (O2•−) were generated using the hypoxanthine–xanthine oxidase system, with nitro blue tetrazolium chloride serving as the detecting system. A significant boost in the SOD-like activity was found via the addition of an electrolyte to the as-prepared nanomaterial solution. The effect of the electrolyte cation (Na+ and K+), as well as its counterion (Cl−, CH3COO−, and H2PO4−/HPO42−) were analyzed. Based on these studies, a new formulation for the preparation of the carbon-based nanomaterial was established. It was demonstrated that the SOD-like activity follows an enzyme-type catalytic activity rather than the stoichiometric scavenging of the superoxide anion radical. It was concluded that 12.71 µg/mL of the EHC nanomaterial exhibits catalytic activity comparable to 15.46 µg/mL of the native Cu/Zn-SOD enzyme. This study provides a starting point for the development of a new nanotool to fight the oxidative stress associated with pathophysiological conditions where SOD activity is depleted. [ABSTRACT FROM AUTHOR]

[Display omitted] The industrial applications of enzymes are usually hindered by the high production cost, intricate reusability, and low stability in terms of thermal, pH, salt, and storage. Therefore, the de novo design of nanozymes that possess the enzyme mimicking biocatalytic functions sheds new light on this field. Here, we propose a facile one-pot synthesis approach to construct Cu-chelated polydopamine nanozymes (PDA-Cu NPs) that can not only catalyze the chromogenic reaction of 2,4-dichlorophenol (2,4-DP) and 4-aminoantipyrine (4-AP), but also present enhanced photothermal catalytic degradation for typical textile dyes. Compared with natural laccase, the designed mimic has higher affinity to the substrate of 2,4-DP with K m of 0.13 mM. Interestingly, PDA-Cu nanoparticles are stable under extreme conditions (temperature, ionic strength, storage), are reusable for 6 cycles with 97 % activity, and exhibit superior substrate universality. Furthermore, PDA-Cu nanozymes show a remarkable acceleration of the catalytic degradation of dyes, malachite green (MG) and methylene blue (MB), under near-infrared (NIR) laser irradiation. These findings offer a promising paradigm on developing novel nanozymes for biomedicine, catalysis, and environmental engineering. [ABSTRACT FROM AUTHOR]

Background: The incidence of osteochondral defects caused by trauma, arthritis or tumours is increasing annually, but progress has not been made in terms of treatment methods. Due to the heterogeneous structure and biological characteristics of cartilage and subchondral bone, the integration of osteochondral repair is still a challenge. Results: In the present study, a novel bilayer hydrogel scaffold was designed based on anatomical characteristics to imitate superficial cartilage and subchondral bone. The scaffold showed favourable biocompatibility, and the addition of an antioxidant nanozyme (LiMn2O4) promoted reactive oxygen species (ROS) scavenging by upregulating antioxidant proteins. The cartilage layer effectively protects against chondrocyte degradation in the inflammatory microenvironment. Subchondral bionic hydrogel scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) by regulating the AMPK pathway in vitro. Finally, an in vivo rat preclinical osteochondral defect model confirmed that the bilayer hydrogel scaffold efficiently promoted cartilage and subchondral bone regeneration. Conclusions: In general, our biomimetic hydrogel scaffold with the ability to regulate the inflammatory microenvironment can effectively repair osteochondral defects. This strategy provides a promising method for regenerating tissues with heterogeneous structures and biological characteristics. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome‐based cell‐free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell‐free and platinum‐based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70–90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications. [ABSTRACT FROM AUTHOR]

Carbon‐based nanozymes have received considerable attention due to their superior biosafety, enhanced tolerance to extreme conditions, and ease of chemical modification. However, due to limited material diversity and unconfirmed molecular structure, carbon‐based nanozymes face challenges such as relatively low enzyme activity and unclear catalytic mechanisms. The development of materials with well‐defined structures and controllable properties is crucial for promoting the rapid progress of nanozymes. Herein, 3,4,9,10‐perylenetetracarboxylic dianhydride (PD) exhibits both glucose oxidase (GOx)‐like and catalase (CAT)‐like activities, which may be due to the fact that PD possesses the features of highly conjugated structure and high electron mobility. In addition, it is demonstrated that the enzymatic activity is related to the degree of PD aggregation via the characterization of its morphology and size. Based on the excellent GOx‐like and CAT‐like activities of PD, a self‐cascade catalytic system is constructed for application in biofuel cells (BFCs). It is worth mentioning that such BFC still maintains high stability after working for 30 days. Therefore, this study expands the enzyme‐like systems and discovers that nanomaterials with highly conjugated structures and high electron mobility can mimic enzymes. Additionally, the multi‐enzyme activities are utilized to construct self‐cascade systems, which can effectively improve the performance of BFCs. [ABSTRACT FROM AUTHOR]

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H2O2) and glutathione (GSH) have been reported to be associated with a variety of diseases. Therefore, the accurate and rapid determination of H2O2 and GSH was very important. The traditional assay was the colorimetric method, which suffered from the bottleneck of single-mode analysis. In this work, we designed a dual-mode fluorescence and colorimetric sensor for detecting H2O2 and GSH based on bifunctional Fe, Co-CDs, which possessed peroxidase (POD)-mimetic activity and fluorescence property. Concretely, the Fe, Co-CDs catalyzed oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to a blue product (oxTMB) with the help of H2O2, which could be inhibited by GSH. Meanwhile, the fluorescence of Fe, Co-CDs weakened with increasing oxTMB, realizing the fluorescence analysis of H2O2 and GSH. In fluorescence and colorimetric sensors, the detection limit (LOD) of H2O2 could reach as low as 0.54 μM and 0.81 μM, as well as the LOD of GSH was 0.39 and 0.61 μM, respectively. Besides, the smartphone-assisted hydrogel sensor was developed for on-site detection of GSH via color change. This study not only designed a dual-mode sensor for dual-target detection but also provided insights for further exploration of multifunctional nanozymes. [ABSTRACT FROM AUTHOR]

Nanozymes have demonstrated superior properties compared to natural enzymes and traditional artificial enzymes in a variety of fields. Although significant progress has been achieved, it remains challenging to develop nanozymes with an adequate catalytic activity. Herein, we, for the first time, bring cerium oxysulfate cluster (Ce-clusters) materials into nanozyme research by a saturated fatty acid regulation strategy due to their potential catalytic activity. It is found that the saturated fatty acids can control the growth, assembly, and size of Ce-clusters in the coprecipitation process, which can enhance the oxidase-like activity of Ce-clusters. With the increase of the alkyl chain length, the catalytic activity gradually decreases because of the strengthened intermolecular interactions between fatty acids and clusters. Notably, the Ce-clusters synthesized with lauric acid present the highest oxidase-like activity among these Ce-clusters. The catalytic activity of nanozyme follows typical Michaelis–Menten kinetics, and the ·O2– and h+ are the main reactive species produced during the catalytic process. Benefiting from the excellent oxidase-like activity, the resultant nanozyme is successfully applied for reductive molecule colorimetric sensing applications. This study not only introduces Ce-clusters into nanozyme research and enriches the oxidase-mimicking nanozyme family but also provides an extremely simple strategy to enhance the catalytic activity of nanozymes, holding great promise in a wide variety of nanozyme applications. [ABSTRACT FROM AUTHOR]

Hydroxyl radical (·OH) scavenging capacity (HOSC) estimation is essential for evaluating antioxidants, natural extracts, or drugs against clinical diseases. While nanozymes offer advantages in related applications, they still face limitations in activity and selectivity. In response, this work showcases the fabrication of laminarin-modulated osmium (laminarin-Os) nanoclusters (1.45 ± 0.05 nm), functioning as peroxidase-like nanozymes within a colorimetric assay tailored for rational HOSC estimation. This study validates both the characterization and remarkable stability of laminarin-Os. By leveraging the abundant surface negative charges of laminarin-Os and the surface hydroxyls of laminarin, oxidation reactions are facilitated, augmenting laminarin-Os's affinity for 3,3′,5,5′-tetramethylbenzidine (TMB) (KM = 0.04 mM). This enables the laminarin-Os-based colorimetric assay to respond to ·OH more effectively than citrate-, albumin-, or other polysaccharides-based Os. In addition, experimental results also validate the selective peroxidase-like behavior of laminarin-Os under acidic conditions. Antioxidants like ascorbic acid, glutathione, tannic acid, and cysteine inhibit absorbance at 652 nm in the colorimetric platform using laminarin-Os's peroxidase-like activity. Compared with commercial kits, this assay demonstrates superior sensitivity (e.g., responds to ascorbic acid 0.01–0.075 mM, glutathione 1–15 µg/mL, tannic acid 0.5–5 µM, and monoammonium glycyrrhizinate cysteine 1.06–10.63 µM) and HOSC testing for glutathione, tannic acid, and monoammonium glycyrrhizinate cysteine. Overall, this study introduces a novel Os nanozyme with exceptional TMB affinity and ·OH selectivity, paving the way for HOSC estimation in biomedical research, pharmaceutical analysis, drug quality control, and beyond. [ABSTRACT FROM AUTHOR]

The stability of black phosphorene (BP) and its preparation and modification for developing and applying devices have become a hot topic in the interdisciplinary field. We propose ultrasound-electrochemistry co-assisted liquid-phase exfoliation as an eco-friendly one-step method to prepare gold–silver bimetallic nanoparticles (Au−AgNPs)-decorated BP nanozyme for smartphone-based portable sensing of 4-nitrophenol (4-NP) in different water sources. The structure, morphology, composition, and properties of Au−AgNPs−BP nanozyme are characterized by multiple instrumental analyses. Bimetallic salts are induced to efficiently occupy oxidative sites of BP to form highly stable Au−AgNPs−BP nanozyme and guarantee the integrity of the lamellar BP. The electrochemistry shortens the exfoliation time of the BP nanosheet and contributes to the loading efficiency of bimetallic nanoparticles on the BP nanosheet. Au−AgNPs−BP-modified screen-printed carbon electrode coupled with palm-sized smartphone-controlled wireless electrochemical analyzer as a portable wireless intelligent sensing platform was applied to the determination of 4-NP in a linear range of 0.6−10 μM with a limit of detection of 63 nM. It enables on-site determination of 4-NP content in lake water, river water, and irrigation ditch water. This work will provide a reference for an eco-friendly one-step preparation of bimetallic nanoparticle-decorated graphene-like materials as nanozymes and their smartphone-based portable sensing application outdoors. [ABSTRACT FROM AUTHOR]

[Display omitted] Diabetic wounds are characterized by chronic trauma, with long-term non-healing attributed to persistent inflammation and recurrent bacterial infections. Exacerbation of the inflammatory response is largely due to increased levels of reactive oxygen species (ROS). In this study, catalase (CAT) was used as a biological template to synthesize nanozyme-supported natural enzymes (CAT-Mn(SH) x) using a biomimetic mineralization method. Subsequently, polymyxin B (CAT-Mn(SH) x @PMB) was immobilized on its surface through electrostatic assembly. CAT-Mn(SH) x @PMB demonstrates the ability for slow and sustained release of hydrogen sulfide (H 2 S). Finally, CAT-Mn(SH) x @PMB loaded microneedles (MNs) substrate were synthesized using polyvinyl alcohol (PVA) and hydroxyethyl methacrylate (HEMA), and named CAT-(MnSH) x @PMB-MNs. It exhibited enhanced enzyme and antioxidant activities, along with effective antibacterial properties. Validation findings indicate that it can up-regulate the level of M2 macrophages and reduce the level of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Additionally, it promotes angiogenesis and rapid nerve regeneration, thereby facilitating wound healing through its dual anti-inflammatory and antibacterial effects. Hence, this study introduces a time–space tissue-penetrating and soluble microneedle patch with dual anti-inflammatory and antibacterial effects for the treatment of diabetic wounds. [ABSTRACT FROM AUTHOR]

[Display omitted] Single-atom catalysts (SACs) have attracted extensive attention in the field of catalysis due to their excellent catalytic ability and enhanced atomic utilization, but the multi-mode single-atom nanozymes for biosensors remain a challenging issue. In this work, iron-doped carbon dots (Fe CDs) were loaded onto the edges and pores of Mo SACs with nanoflower morphology; accordingly, a composite material Fe CDs/Mo SACs was prepared successfully, which improves the catalytic performance and develops a fluorescence mode without changing the original morphology. The steady-state kinetic data indicates that the material prepared have better affinity for substrates and faster reaction rates under optimized conditions. The specific kinetic parameters K m and V max were calculated as 0.39 mM and 7.502×10−7 M·s−1 respectively. The excellent peroxidase-like activity of Fe CDs/Mo SACs allows H 2 O 2 to decompose into •OH, which in turn oxidizes colorless o -phenylenediamine (OPD) to yellow 2,3-diaminophenazine (DAP). At the same time, the fluorescence signal of Fe CDs/Mo SACs quenches obviously by DAP at 460 nm through internal filtration effect (IFE), while the characteristic fluorescence response of DAP gradually increases at 590 nm. Based on this sensing mechanism, a sensitive and accurate dual-mode (colorimetric and ratiometric fluorescent) sensor was constructed to detect H 2 O 2 and uric acid, and the rate of recovery and linearity were acceptable for the detection of UA in human serum and urine samples. This method provides a new strategy for rapid and sensitive detection of UA, and also broadens the development of SACs in the field of biosensors. [ABSTRACT FROM AUTHOR]

Tumor microenvironment (TME)‐responsive nanozymes‐based catalytic therapy shows great potential in combating malignant tumor. However, their biological application still suffers from deficient catalytic activity. Herein, the MoOx‐Rh metallene nanozyme demonstrates highly efficient multiple enzymatic catalytic activities, where MoOx species atomically dispersed on Rh metallene surface. The resulting structures enable MoOx‐Rh metallene with maximally exposed active oxide‐metallene interface and more atoms sites around interface can be well finely regulated. Results of experiment and density functional theory (DFT) simulations support the notion that atomic interface structure facilitates multiple enzyme‐like reactions. As a TME‐responsive nanozyme, MoOx‐Rh metallene exhibits remarkable therapeutic effect of tumor due to intrinsic near‐infrared photothermal effect and laser‐enhanced multiple enzymatic catalytic activities. This study illustrates the great promise of atomic interface engineering strategy in tumor catalytic therapy. [ABSTRACT FROM AUTHOR]

Light-drive hydrogen production using titanium-based perovskite is one sustainable way to reduce current reliance on fossil fuels, but its wide applications are still limited by high electron–hole recombination and sluggish surface reaction. Thus, the developments for low-cost and highly efficient co-catalysts remain urgent. Inspired by natural [NiFe]-hydrogenase active center structure, a hydrogenase-mimic, NiCo2S4 nanozyme was synthesized, and subsequently decorated onto the CaTiO3 to catalyze the hydrogen evolution reaction (HER). Among the following test, CaTiO3 with a 15% loading of NiCo2S4 nanozyme exhibited the highest HER rate of 307.76 µmol·g−1·h−1, which is 60 times higher than that of the CaTiO3 alone. The results reveal that NiCo2S4 not only significantly increased the charge separation efficiency of the photogenerated carriers, but also substantively lowered the HER activation energy. Mechanism studies show that NiCo2S4 readily splits H2O by forming the Ni(OH)-Co intermediate and only Ni in the bimetallic center alters the oxidation state during the HER process in a manner analogous to the [NiFe]-hydrogenase. In contrast to the often-expensive synthetic catalysts that rely on rare elements such as ruthenium and platinum, this study shows a promising way to develop the nature-inspired cocatalysts to enhance the photocatalysts' HER performance. [ABSTRACT FROM AUTHOR]

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The effects of an increasingly elderly population are among the most far-reaching in 21st-century society. The growing healthcare expense is mainly attributable to the increased incidence of chronic illnesses that accompany longer life expectancies. Different ideas have been put up to explain aging, but it is widely accepted that oxidative damage to proteins, lipids, and nucleic acids contributes to the aging process. Increases in life expectancy in all contemporary industrialized cultures are accompanied by sharp increases in the prevalence of age-related diseases such as cardiovascular and neurological conditions, type 2 diabetes, osteoporosis, and cancer. Therefore, academic and public health authorities should prioritize the development of therapies to increase health span. Nanozyme (NZ)-like activity in nanomaterials has been identified as promising anti-aging nanomedicines. More than that, nanomaterials displaying catalytic activities have evolved as artificial enzymes with high structural stability, variable catalytic activity, and functional diversity for use in a wide range of biological settings, including those dealing with age-related disorders. Due to their inherent enzyme-mimicking qualities, enzymes have attracted significant interest in treating diseases associated with reactive oxygen species (ROS). The effects of NZs on aging and age-related disorders are summarized in this article. Finally, prospects and threats to enzyme research and use in aging and age-related disorders are offered. [ABSTRACT FROM AUTHOR]

Pheochromocytoma may be overlooked or misdiagnosed in its early stages, resulting in serious clinical consequences. To comprehensively and accurately diagnose pheochromocytoma, we established a smartphone-assisted colorimetric sensing platform for the determination of two biomarkers of pheochromocytoma: epinephrine (Epi) and glutathione (GSH). In this article, Co/Mn-doped oxide nanosheets (CoMnNSs) with oxidase-like and laccase-like activities have been synthesized via a one-step process. Compared to MnO2 nanosheets (MnO2 NSs), CoMnNSs have stronger catalytic activity due to the doping of the transition metal Co. Under optimal conditions, the oxidase-like and laccase-like activities of CoMnNSs were utilized for the determination of GSH and Epi, respectively, and the assay could be completed within 3 min, with the limits of detection (LOD) of 0.15 and 0.52 μM, respectively. Besides, the practicability of the established approach was confirmed in human serum samples with satisfactory recoveries. The experimental results indicated that the designed sensor demonstrated excellent sensitivity and selectivity. Thus, this work not only widens the idea for early visual diagnosis of pheochromocytoma but also confirms the effectiveness of the transition-metal doping strategy, which offers a simple, economical, and gentle means of modulating nanozyme activity. [ABSTRACT FROM AUTHOR]

Reducing substances play crucial roles in various physiological processes and serve as essential components in the antioxidant defense mechanisms within organisms. Nonetheless, accurately detecting and distinguishing between these substances present a notable challenge due to the presence of potential interferences in complex samples. In response to this challenge, a novel multisignal sensing platform and sensor array have been developed, leveraging fluorescent polydopamine nanoparticles (FPDA) and MnO2 nanozyme. The MnO2/FPDA nanoplatform possesses exceptional catalytic activity and the ability to modulate ratiometric fluorescence in the presence of o-phenylenediamine (OPD), offering a platform with dual-channel output signals in ratiometric fluorescence and UV absorbance. Upon introduction of H2O2, the MnO2 undergoes transformation into Mn2+, thereby reducing the oxidase-like activity of MnO2 and reinstating the fluorescence of FPDA. Notably, this platform exhibits detection ranges for H2O2 from 5 to 500 and 15 to 500 μM, with corresponding detection limits of 3.18 and 10.67 μM using fluorescence and colorimetric channels, respectively. This setup has been deployed for quantifying H2O2 in milk and cell lysates, showcasing its versatility as a universal analysis tool for other reducing agents like ascorbic acid. Furthermore, a sensor array has been developed based on MnO2/FPDA/OPD, demonstrating a robust capacity to effectively differentiate and identify five reducing agents effectively. This sensor array also exhibits strong performance in discriminating reducing substances within intricate or authentic samples, such as oranges and cell lysates, underscores its practical utility. This study offers significant insights into the development of sensing platforms for the selectively detecting specific reducing species in real samples or deploying sensor arrays for distinguishing multiple components within authentic samples. Such advancements pave the way for enhanced analysis and screening of reducing substances in cellular and food samples. [ABSTRACT FROM AUTHOR]

The development of nanozymes has emerged as a promising pathway for combating bacterial infections. In this work, Ag/Schiff base nanozymes are obtained through the in situ reduction method on [2 + 3] Schiff base macrocycles using eco-friendly reductant α-tocopherol. The silver prepared was found to be nanoscale by TEM, and Ag NPs grew and dispersed uniformly on the surface of the Schiff base macrocycle due to the abundance of the CN double bonds. The peroxidase-like catalytic activity of the Ag/Schiff base was evaluated toward 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, and the Km values of 0.350 and 0.090 mM confirm the strong affinity of Ag/Schiff base for H2O2 and TMB. Moreover, the nanozyme exhibited good antibacterial properties against Streptococcus sanguinis, Pseudomonas aeruginosa, and Staphylococcus aureus, and in vivo tests confirmed that the Ag/Schiff base had negligible biotoxicity. Benefiting from the good antimicrobial and biosafety properties, the nanozymes were explored to prepare antibacterial films, and the bacterial inhibition zones demonstrated that the introduction of the Ag/Schiff base could prevent the growth of bacteria. [ABSTRACT FROM AUTHOR]

Chiral molecules have similar physicochemical properties, which are different in terms of physiological activities and toxicities, rendering their differentiation and recognition highly significant. Nanozymes, which are nanomaterials with inherent enzyme-like activities, have garnered significant interest owing to their high cost-effectiveness, enhanced stability, and straightforward synthesis. However, constructing nanozymes with high activity and enantioselectivity remains a significant challenge. This review briefly introduces the synthesis methods of chiral nanozymes and systematically summarizes the latest research progress in enantioselective recognition of chiral molecules based on electrochemical methods and ultraviolet–visible absorption spectroscopy. Moreover, the challenges and development trends in developing enantioselective nanozymes are discussed. It is expected that this review will provide new ideas for the design of multifunctional chiral nanozymes and broaden the application field of nanozymes. [ABSTRACT FROM AUTHOR]

The advancement of nanozymes with oxidase-initiating activity that are affordable and stable is essential for real-time monitoring in biosensors, medicine, and environmental protection and remains a significant challenge. Covalent organic framework (COF) is an emerging type of crystalline porous organic framework material that is constructed from organic building units by covalent bonds. In this study, we successfully synthesized three isoreticular two-dimensional (2D) COFs by choosing diarylamino-benzene-based tetra-amines to construct [4 + 4]-type COFs. The resultant COFs exhibited excellent oxidase-mimicking activity under light stimulation, which can catalyze the oxidation of tetramethylbenzydine (TMB) by the formation of O2•– free radicals under an open-air condition. A sensitive sensor was designed based on the oxidase-mimicking activity of these COFs for the determination of glutathione (GSH) in real samples, achieving a detection limit of 0.22 μM, outperforming the standard materials studied in GSH detection within reticular frameworks. This work offers possibilities for investigating the oxidase-initiating activity of nanozymes and broadening the utilization of COFs in the realm of biosensing. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is a leading intraocular malignancy with a high 5‐year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe‐layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types. [ABSTRACT FROM AUTHOR]

Since the discovery of the first peroxidase nanozyme (Fe3O4), numerous nanomaterials have been reported to exhibit intrinsic enzyme‐like activity toward inorganic oxygen species, such as H2O2, oxygen, and O2−. However, the exploration of nanozymes targeting organic compounds holds transformative potential in the realm of industrial synthesis. This review provides a comprehensive overview of the diverse types of nanozymes that catalyze reactions involving organic substrates and discusses their catalytic mechanisms, structure‐activity relationships, and methodological paradigms for discovering new nanozymes. Additionally, we propose a forward‐looking perspective on designing nanozyme formulations to mimic subcellular organelles, such as chloroplasts, termed “nano‐organelles”. Finally, we analyze the challenges encountered in nanozyme synthesis, characterization, nano‐organelle construction and applications while suggesting directions to overcome these obstacles and enhance nanozyme research in the future. Through this review, our goal is to inspire further research efforts and catalyze advancements in the field of nanozymes, fostering new insights and opportunities in chemical synthesis. [ABSTRACT FROM AUTHOR]

Lubricin, secreted primarily by chondrocytes, plays a critical role in maintaining the function of the cartilage lubrication system. However, both external factors such as friction and internal factors like oxidative stress can disrupt this system, leading to osteoarthritis. Inspired by lubricin, a lubricating nanozyme, that is, Poly‐2‐acrylamide‐2‐methylpropanesulfonic acid sodium salt‐grafted aminofullerene, is developed to restore the cartilage lubrication system using an “In‐Out” strategy. The “Out” aspect involves reducing friction through a combination of hydration lubrication and ball‐bearing lubrication. Simultaneously, the “In” aspect aims to mitigate oxidative stress by reducing free radical, increasing autophagy, and improving the mitochondrial respiratory chain. This results in reduced chondrocyte senescence and increased lubricin production, enhancing the natural lubrication ability of cartilage. Transcriptome sequencing and Western blot results demonstrate that it enhances the functionality of mitochondrial respiratory chain complexes I, III, and V, thereby improving mitochondrial function in chondrocytes. In vitro and in vivo experiments show that the lubricating nanozymes reduce cartilage wear, improve chondrocyte senescence, and mitigate oxidative stress damage, thereby mitigating the progression of osteoarthritis. These findings provide novel insights into treating diseases associated with oxidative stress and frictional damage, such as osteoarthritis, and set the stage for future research and development of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Despite decades of research, Parkinson's disease is still an idiopathic pathology for which no cure has yet been found. This is partly explained by the multifactorial character of most neurodegenerative syndromes, whose generation involves multiple pathogenic factors. In Parkinson's disease, two of the most important ones are the aggregation of α‐synuclein and oxidative stress. In this work, we address both issues by synthesizing a multifunctional nanozyme based on grafting a pyridinophane ligand that can strongly coordinate CuII, onto biodegradable PEGylated polyester nanoparticles. The resulting nanozyme exhibits remarkable superoxide dismutase activity together with the ability to inhibit the self‐induced aggregation of α‐synuclein into amyloid‐type fibrils. Furthermore, the combination of the chelator and the polymer produces a cooperative effect whereby the resulting nanozyme can also halve CuII‐induced α‐synuclein aggregation. [ABSTRACT FROM AUTHOR]

Bimetallic nanomaterials have generated significant interest across diverse scientific disciplines, due to their unique and tunable properties arising from the synergistic combination of two distinct metallic elements. This study presents a novel approach for synthesizing branched gold–platinum nanoparticles by utilizing poly(allylamine hydrochloride) (PAH)-stabilized branched gold nanoparticles, with a localized surface plasmon resonance (LSPR) response of around 1000 nm, as a template for platinum deposition. This approach allows precise control over nanoparticle size, the LSPR band, and the branching degree at an ambient temperature, without the need for high temperatures or organic solvents. The resulting AuPt branched nanoparticles not only demonstrate optical activity but also enhanced catalytic properties. To evaluate their catalytic potential, we compared the enzymatic capabilities of gold and gold–platinum nanoparticles by examining their peroxidase-like activity in the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB). Our findings revealed that the incorporation of platinum onto the gold surface substantially enhanced the catalytic efficiency, highlighting the potential of these bimetallic nanoparticles in catalytic applications. [ABSTRACT FROM AUTHOR]

Copper-cobalt bimetallic nitrogen-doped carbon-based nanoenzymatic materials (CuCo@NC) were synthesized using a one-step pyrolysis process. A three-channel colorimetric sensor array was constructed for the detection of seven antioxidants, including cysteine (Cys), uric acid (UA), tea polyphenols (TP), lysine (Lys), ascorbic acid (AA), glutathione (GSH), and dopamine (DA). CuCo@NC with peroxidase activity was used to catalyze the oxidation of TMB by H2O2 at three different ratios of metal sites. The ability of various antioxidants to reduce the oxidation products of TMB (ox TMB) varied, leading to distinct absorbance changes. Linear discriminant analysis (LDA) results showed that the sensor array was capable of detecting seven antioxidants in buffer and serum samples. It could successfully discriminate antioxidants with a minimum concentration of 10 nM. Thus, multifunctional sensor arrays based on CuCo@NC bimetallic nanoenzymes not only offer a promising strategy for identifying various antioxidants but also expand their applications in medical diagnostics and environmental analysis of food. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Sichuan University (Medical Science Edition) is the property of Editorial Board of Journal of Sichuan University (Medical Sciences) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Sichuan University (Medical Science Edition) is the property of Editorial Board of Journal of Sichuan University (Medical Sciences) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The design and development of nanomaterials with intrinsic enzyme‐like activities (nanozymes) have attracted huge interest during the past several decades. Herein, by incorporating the concept of nanozyme‐involved biomimetic catalysis into the molecular assembly, we introduce an exciting example of utilizing the gold nanozyme system to expedite the sol‐gel transition of silk fibroin. In this system, silica‐encapsulated gold nanoparticles (MSN‐AuNPs) possess an intrinsic glucose oxidase‐like activity, and the activity of AuNPs has been studied by using first‐principles calculations. The catalytic oxidization of glucose into gluconic acid by MSN‐AuNPs leads to a significant decrease in the pH value of silk fibroin solution, rapidly accelerating the self‐assembly of silk fibroin solution into physical hydrogel. Since nanozymes can be further remotely controlled via different stimuli, this simple, rational control and accelerated method is a significant breakthrough, will lead to a large pool of opportunities for further exploration of nanozymes in the field of molecular assembly. [ABSTRACT FROM AUTHOR]

Misusage of tetracycline (TC) antibiotics residue in animal food has posed a significant threat to human health. Therefore, there is an urgent need to develop highly sensitive and robust assays for detecting TC. In the current study, gold and platinum nanoparticles were deposited on carbon nanotubes (CNTs) through the superposition method (Au@Pt/CNTs-s) and one-pot method (Au@Pt/CNTs-o). Au@Pt/CNTs-s displayed higher enzyme-like activity than Au@Pt/CNTs-o, which were utilized for the development of sensitive magnetic immunoassays. Under the optimized conditions, the limits of detection (LODs) of magnetic immunoassays assisted by Au@Pt/CNTs-s and Au@Pt/CNTs-o against TCs could reach 0.74 ng/mL and 1.74 ng/m, respectively, which were improved 6-fold and 2.5-fold in comparison with conventional magnetic immunoassay. In addition, the measurement of TC-family antibiotics was implemented by this assay, and ascribed to the antibody used that could recognize TC, oxytetracycline, chlortetracycline, and doxycycline with high cross-reactivity. Furthermore, the method showed good accuracy (recoveries, 92.1–114.5% for milk; 88.6–92.4% for pork samples), which also were applied for determination of the targets in real samples. This study provides novel insights into the rapid detection of targets based on high-performance nanocatalysts. [ABSTRACT FROM AUTHOR]

Abstract Preserving pulp viability and promoting pulp regeneration in pulpitis have attracted widespread attention. Restricted by the oxidative stress microenvironment of dental pulpitis, excessive reactive oxygen and nitrogen species (RONS) trigger uncontrolled inflammation and exacerbate pulp tissue destruction. However, modulating redox homeostasis in inflamed pulp tissue to promote pulp regeneration remains a great challenge. Herein, this work proposes an effective antioxidative system (C-NZ/GelMA) consisting of carbon dot nanozymes (C-NZ) with gelatin methacryloyl (GelMA) to modulate the pulpitis microenvironment for dental pulp regeneration by utilizing the antioxidant properties of C-NZ and the mechanical support of an injectable GelMA hydrogel. This system effectively scavenges RONS to normalize intracellular redox homeostasis, relieving oxidative stress damage. Impressively, it can dramatically enhance the polarization of regenerative M2 macrophages. This study revealed that the C-NZ/GelMA hydrogel promoted pulp regeneration and dentin repair through its outstanding antioxidant, antiapoptotic, and anti-inflammatory effects, suggesting that the C-NZ/GelMA hydrogel is highly valuable for pulpitis treatment.

As an important part of food quality management, the detection of food hazard factors and safety risk prediction have always been a research hotspot. In order to better carry out related work in the future, this article reviews research progress on conventional methods for the detection of food hazard factors, and introduces new methods for the detection of food hazard factors such as nanozymes, clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR/Cas) sensors and nuclear magnetic resonance (NMR) spectroscopy and the application of new materials such as magnetic covalent organic frameworks in this field. Then, it summarizes the application of subjective weighting, machine learning and deep learning in food safety risk prediction. Finally, the advantages and disadvantages of each method are analyzed, and future research directions are discussed.

Abstract Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.

Hailing Yu,1,* Yongquan Huang,2,* Zhisheng Nong,3,* Xi Lin,1 Kexin Tang,1 Zeyu Cai,1 Kaichen Huang,4 Ting Yu,1 Huimin Lan,1 Qianqian Zhang,1 Qiang Wang,5 Lei Yang,6 Jingchuan Zhu,7 Lili Wu,8 Hui Luo1 1Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3School of Materials Science and Engineering, Shenyang Aerospace University, Shenyang, Liaoning, People’s Republic of China; 4Department of Clinical laboratory, The Third People’s Hospital of Zhuhai, Zhuhai, Guangdong, People’s Republic of China; 5The Green Aerotechnics Research Institute of Chongqing Jiaotong University, Chongqing, People’s Republic of China; 6Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 7School of Materials Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 8Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, School of Physics and Electronic Engineering, Harbin Normal University, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Luo; Lili Wu, Email luoh53@mail.sysu.edu.cn; wll790107@hotmail.comIntroduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo.Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth.Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment.Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.Keywords: nanozyme, sonodynamic therapy, Ti3C2/TiO2, ROS

Abstract Background The incidence of osteochondral defects caused by trauma, arthritis or tumours is increasing annually, but progress has not been made in terms of treatment methods. Due to the heterogeneous structure and biological characteristics of cartilage and subchondral bone, the integration of osteochondral repair is still a challenge. Results In the present study, a novel bilayer hydrogel scaffold was designed based on anatomical characteristics to imitate superficial cartilage and subchondral bone. The scaffold showed favourable biocompatibility, and the addition of an antioxidant nanozyme (LiMn2O4) promoted reactive oxygen species (ROS) scavenging by upregulating antioxidant proteins. The cartilage layer effectively protects against chondrocyte degradation in the inflammatory microenvironment. Subchondral bionic hydrogel scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) by regulating the AMPK pathway in vitro. Finally, an in vivo rat preclinical osteochondral defect model confirmed that the bilayer hydrogel scaffold efficiently promoted cartilage and subchondral bone regeneration. Conclusions In general, our biomimetic hydrogel scaffold with the ability to regulate the inflammatory microenvironment can effectively repair osteochondral defects. This strategy provides a promising method for regenerating tissues with heterogeneous structures and biological characteristics. Graphical abstract

The abundance of molecules on early Earth likely enabled a wide range of prebiotic chemistry, with peptides playing a key role in the development of early life forms and the evolution of metabolic pathways. Among peptides, those with enzyme-like activities occupy a unique position between peptides and enzymes, combining both structural flexibility and catalytic functionality. However, their full potential remains largely untapped. Further exploration of these enzyme-like peptides at the nanoscale could provide valuable insights into modern nanotechnology, biomedicine, and even the origins of life. Hence, this review introduces the groundbreaking concept of “peptide nanozymes (PepNzymes)”, which includes single peptides exhibiting enzyme-like activities, peptide-based nanostructures with enzyme-like activities, and peptide-based nanozymes, thus enabling the investigation of biological phenomena at nanoscale dimensions. Through the rational design of enzyme-like peptides or their assembly with nanostructures and nanozymes, researchers have found or created PepNzymes capable of catalyzing a wide range of reactions. By scrutinizing the interactions between the structures and enzyme-like activities of PepNzymes, we have gained valuable insights into the underlying mechanisms governing enzyme-like activities. Generally, PepNzymes play a crucial role in biological processes by facilitating small-scale enzyme-like reactions, speeding up molecular oxidation-reduction, cleavage, and synthesis reactions, leveraging the functional properties of peptides, and creating a stable microenvironment, among other functions. These discoveries make PepNzymes useful for diagnostics, cellular imaging, antimicrobial therapy, tissue engineering, anti-tumor treatments, and more while pointing out opportunities. Overall, this research provides a significant journey of PepNzymes’ potential in various biomedical applications, pushing them towards new advancements.

Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries. Corneal scars such as leukoplakia are formed due to inflammation, oxidative stress and non-directed repair, which seriously affect the patients' subsequent visual and life quality. In this study, drawing inspiration from the oriented structure of collagen fibers within the corneal stroma, we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning. It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer. The results showed that it effectively inhibited Candida albicans, Aspergillus Niger, Fusarium sapropelum, which mainly affects TNF, NF-kappa B, and HIF-1 signaling pathways, achieving effective antifungal functions. More importantly, the fibroblasts interacted with extracellular matrix (ECM) of corneal stroma through formation of focal adhesions, promoted the proliferation and directional migration of cells in vitro, induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo. This process is mainly associated with MYLK, MYL9, and ITGA3 molecules. Furthermore, the downregulation the growth factors TGF-β and PDGF-β inhibits myofibroblast development and reduces scar-type ECM production, thereby reducing corneal leukoplakia. It also activates the PI3K-AKT signaling pathway, promoting corneal healing. In conclusion, the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers, inhibits inflammation, eliminates reactive oxygen species, and reduces corneal leukoplakia, which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.

[Display omitted] • pH-Responsive injectable self-healing hydrogel was prepared. • Au NPs-decorated Ti/Fe bimetallic organic frameworks were loaded in the hydrogel. • The hydrogel exhibited pH-responsive release of drugs and therapeutic agents. • The nanocomposite hydrogel shows SDT-CDT-ST-CT synergistic therapy against cancer. A novel and efficient cancer therapy was developed using a smart hydrogel containing multifunctional bimetallic organic frameworks and anticancer drugs. The injectable self-healing hydrogel with pH-responsiveness was constructed through borate ester and imine bonds among dopamine-grafted sodium alginate (SADA), hydroxypropyl chitosan (HPCS) and 2-formylphenylboronic acid (2-FPBA). The Au nanoparticles-decorated Ti/Fe bimetallic organic framework tetragonal nanosheets (Au/TF-MOF TNS) were synthesized and incorporated into the hydrogel with the anticancer drugs doxorubicin (DOX). Upon intratumoral injection of nanocomposite hydrogel, the acidic tumor microenvironment triggered the cleavage of borate ester and imine bonds, causing the hydrogel to break down and accelerating the release of both Au/TF-MOF TNS and DOX. These Au/TF-MOF TNS functioned as nanozymes, producing hydroxyl radicals (·OH) for chemodynamic therapy (CDT), generating oxygen (O 2) to support sonodynamic therapy (SDT), and depleting glucose for starvation therapy (ST). Additionally, the Au/TF-MOF TNS served as sonosensitizers, capable of converting O 2 into singlet oxygen (1O 2) upon ultrasound irradiation to achieve SDT. Therefore, this nanocomposite hydrogel system enabled synergistic sonodynamic-chemodynamic-starvation-chemo therapy (SDT-CDT-ST-CT) of cancer, presenting a promising platform for advanced cancer therapy strategies. [ABSTRACT FROM AUTHOR]

Abstract Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Abstract Nanozyme, characterized by outstanding and inherent enzyme-mimicking properties, have emerged as highly promising alternatives to natural enzymes owning to their exceptional attributes such as regulation of oxidative stress, convenient storage, adjustable catalytic activities, remarkable stability, and effortless scalability for large-scale production. Given the potent regulatory function of nanozymes on oxidative stress and coupled with the fact that reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of metabolic diseases, nanozyme offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of metabolic diseases by directly scavenging excess ROS or regulating pathologically related molecules. The rational design strategies, nanozyme-enabled therapeutic mechanisms at the cellular level, and the therapies of nanozyme for several typical metabolic diseases and underlying mechanisms are discussed, mainly including obesity, diabetes, cardiovascular disease, diabetic wound healing, and others. Finally, the pharmacokinetics, safety analysis, challenges, and outlooks for the application of nanozyme are also presented. This review will provide some instructive perspectives on nanozyme and promote the development of enzyme-mimicking strategies in metabolic disease therapy. Graphical Abstract

Numerous local herbal extract species have been investigated as potential medicinal ingredients due to their promising anti-cancer properties. However, the primary constraint of the class of plant flavonoids lies in their low solubility and limited membrane permeability, leading to chemical instability and restricted bioavailability that impede biomedical applications. In this study, we have developed an ideal nanozyme-Galazyme, comprising galangin-loaded copper Nanozyme coated by DSPE-PEG, which amplifies oxidative stress to induce apoptosis via the regulation of reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) activation. Galazyme exhibited significant peroxidase mimetic activity, demonstrating its potential to generate ROS and elevate oxidative stress. Upon uptake by HepG-2 cells, Galazyme efficiently converts excess hydrogen peroxide (H2O2) into highly reactive -OH radicals and upregulates MAPK expression, leading to the activation of Bax and Caspase 3, thereby promoting irreversible tumor cell apoptosis. Both in vitro and in vivo results demonstrate that Galazyme inhibits tumor cell growth and induces apoptosis by generating ample ROS and activating the MAPK pathway. Our study offers novel evidence supporting the enhancement of Galazyme-induced apoptosis through the upregulation of Bax and Caspase 3, along with the elucidation of the interaction between MAPK and apoptosis. [ABSTRACT FROM AUTHOR]

Bacterial therapy is recognized as a cost‐effective treatment for several diseases. However, its development is hindered by limited functionality, weak inherent therapeutic effects, and vulnerability to harsh microenvironmental conditions, leading to suboptimal treatment activity. Enhancing bacterial activity and therapeutic outcomes emerges as a pivotal challenge. Nanozymes have garnered significant attention due to their enzyme‐mimic activities and high stability. They enable bacteria to mimic the functions of gene‐edited bacteria expressing the same functional enzymes, thereby improving bacterial activity and therapeutic efficacy. This review delineates the therapeutic mechanisms of bacteria and nanozymes, followed by a summary of strategies for preparing bacteria/nanozyme composites. Additionally, the synergistic effects of such composites in biomedical applications such as gastrointestinal diseases and tumors are highlighted. Finally, the challenges of bacteria/nanozyme composites are discussed and propose potential solutions. This study aims to provide valuable insights to offer theoretical guidance for the advancement of nanomaterial‐assisted bacterial therapy. [ABSTRACT FROM AUTHOR]