Photoexcited Ru single-atomic sites for efficient biomimetic redox catalysis.

The unsatisfactory catalytic activity of nanozymes owing to their inefficient electron transfer (ET) is the major challenge in biomimetic catalysis-related biomedical applications. Inspired by the photoelectron transfers in natural photoenzymes, we herein report a photonanozyme of single-atom Ru anchored on metal-organic frameworks (UiO-67-Ru) for achieving photoenhanced peroxidase (POD)-like activity. We demonstrate that the atomically dispersed Ru sites can realize high photoelectric conversion efficiency, superior POD-like activity (7.0-fold photoactivity enhancement relative to that of UiO-67), and good catalytic specificity. Both in situ experiments and theoretical calculations reveal that photoelectrons follow the cofactor-mediated ET process of enzymes to promote the production of active intermediates and the release of products, demonstrating more favorable thermodynamics and kinetics in H2O2 reduction. Taking advantage of the unique interaction of the Zr-O-P bond, we establish a UiO-67-Ru-based immunoassay platform for the photoenhanced detection of organophosphorus pesticides.

Nanozyme-Enhanced Probiotic Spores Regulate the Intestinal Microenvironment for Targeted Acute Gastroenteritis Therapy.

Antibiotic therapeutics to combat intestinal pathogen infections often exacerbate microbiota dysbiosis and impair mucosal barrier functions. Probiotics are promising strategies, because they inhibit pathogen colonization and improve intestinal microbiota imbalance. Nevertheless, their limited targeting ability and susceptibility to oxidative stress have hindered their therapeutic potential. To tackle these challenges, Ces3 is synthesized by in situ growth of CeO2 nanozymes with positive charges on probiotic spores, facilitating electrostatic interactions with negatively charged pathogens and possessing a high reactive oxygen species (ROS) scavenging activity. Importantly, Ces3 can resist the harsh environment of the gastrointestinal tract. In mice with S. Typhimurium-infected acute gastroenteritis, Ces3 shows potent anti-S. Typhimurium activity, thereby alleviating the dissemination of S. Typhimurium into other organs. Additionally, owing to its O2 deprivation capacity, Ces3 promotes the proliferation of anaerobic probiotics, reshaping a healthy intestinal microbiota. This work demonstrates the promise of combining antibacterial, anti-inflammatory, and O2 content regulation properties for acute gastroenteritis therapy.

Artificial-Cofactor-Mediated Hydrogen and Electron Transfer Endows AuFe/Polydopamine Superparticles with Enhanced Glucose Oxidase-Like Activity.

Various applications related to glucose catalysis have led to the development of functional nanozymes with glucose oxidase (GOX)-like activity. However, the unsatisfactory catalytic activity of nanozymes is a major challenge for their practical applications due to their inefficient hydrogen and electron transfer. Herein, we present the synthesis of AuFe/polydopamine (PDA) superparticles that exhibit photothermal-enhanced GOX-like activity. Experimental investigations and theoretical calculations reveal that the glucose oxidation process catalyzed by AuFe/PDA follows an artificial-cofactor-mediated hydrogen atom transfer mechanism, which facilitates the generation of carbon-centered radical intermediates. Rather than depending on charged Au surfaces for thermodynamically unstable hydride transfer, Fe(III)-coordinated PDA with abundant amino and phenolic hydroxyl groups serves as cofactor mimics, facilitating both hydrogen atom and electron transfer in the catalytic process. Finally, leveraging the photothermal-enhanced GOX-like and catalase-like activities of AuFe/PDA, we establish a highly sensitive and accurate point-of-care testing blood glucose determination with exceptional anti-jamming capabilities.

Grain-Boundary-Rich Ceria Metallene Nanozyme with Abundant Metal Site Pairs Boosts Phosphatase-like Activity.

Natural phosphatases featuring paired metal sites inspire various advanced nanozymes with phosphatase-like activity as alternatives in practical applications. Numerous efforts to create point defects show limited metal site pairs, further resulting in insufficient activity. However, it remains a grand challenge to accurately engineer abundant metal site pairs in nanozymes. Herein, we report a grain-boundary-rich ceria metallene nanozyme (GB-CeO2) with phosphatase-like activity. Grain boundaries acting as the line or interfacial defects can effectively increase the content of Ce4+/Ce3+ site pairs to 72.28%, achieving a 49.28-fold enhancement in activity. Furthermore, abundant grain boundaries optimize the band structure to assist the photoelectron transfer under irradiation, which further increases the content of metal site pairs to 88.96% and finally realizes a 114.39-fold enhanced activity over that of CeO2 without irradiation. Given the different inhibition effects of pesticides on catalysts with and without irradiation, GB-CeO2 was successfully applied to recognize mixed toxic pesticides.

Nanozyme Metabolism Controls Air Pollution over an Atomic Potassium Cyano Site.

Increasing threats of air pollution prompt the design of air purification systems. As a promising initiative defense strategy, nanocatalysts are integrated to catalyze the detoxification of specific pollutants. However, it remains a grand challenge to tailor versatile nanocatalysts to cope with diverse pollutants in practice. Here, we report a nanozyme metabolism system to realize broad-spectrum protection from air pollution. Atomic K-modified carbon nitride featuring flavin oxidase-like and peroxidase-like activities was synthesized to initiate nanozyme metabolism. In situ experiments and theoretical investigations collectively show that K sites optimize the geometric and electronic structure of cyano sites for both enzyme-like activities. As a proof of concept, the nanozyme metabolism was applied to the mask against volatile organic compounds, persistent organic pollutants, reactive oxygen species, bacteria, and so on. Our finding provides a thought to tackle global air pollution and deepens the understanding of nanozyme metabolism.

p-d Orbital Hybridization-Engineered PdSn Nanozymes for a Sensitive Immunoassay.

Nanozymes with peroxidase-like activity have been extensively studied for colorimetric biosensing. However, their catalytic activity and specificity still lag far behind those of natural enzymes, which significantly affects the accuracy and sensitivity of colorimetric biosensing. To address this issue, we design PdSn nanozymes with selectively enhanced peroxidase-like activity, which improves the sensitivity and accuracy of a colorimetric immunoassay. The peroxidase-like activity of PdSn nanozymes is significantly higher than that of Pd nanozymes. Theoretical calculations reveal that the p-d orbital hybridization of Pd and Sn not only results in an upward shift of the d-band center to enhance hydrogen peroxide (H2O2) adsorption but also regulates the O-O bonding strength of H2O2 to achieve selective H2O2 activation. Ultimately, the nanozyme-linked immunosorbent assay has been successfully developed to sensitively and accurately detect the prostate-specific antigen (PSA), achieving a low detection limit of 1.696 pg mL-1. This work demonstrates a promising approach for detecting PSA in a clinical diagnosis.

Improvement in ORR Durability of Fe Single-Atom Carbon Catalysts Hybridized with CeO2 Nanozyme.

FeNC catalysts are considered one of the most promising alternatives to platinum group metals for the oxygen reduction reaction (ORR). Despite the extensive research on improving ORR activity, the undesirable durability of FeNC is still a critical issue for its practical application. Herein, inspired by the antioxidant mechanism of natural enzymes, CeO2 nanozymes featuring catalase-like and superoxide dismutase-like activities were coupled with FeNC to mitigate the attack of reactive oxygen species (ROS) for improving durability. Benefiting from the multienzyme-like activities of CeO2, ROS generated from FeNC is instantaneously eliminated to alleviate the corrosion of carbon and demetallization of metal sites. Consequently, FeNC/CeO2 exhibits better ORR durability with a decay of only 5 mV compared to FeNC (18 mV) in neutral electrolyte after 10k cycles. The FeNC/CeO2-based zinc-air battery also shows minimal voltage decay over 140 h in galvanostatic discharge-charge cycling tests, outperforming FeNC and commercial Pt/C.

Mated-Atom Nanozymes with Efficient Assisted NAD+ Replenishment for Skin Regeneration.

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.

Three-Step Depletion Strategy of Glutathione: Tunable Metal-Organic-Framework-Engineered Nanozymes for Driving Oxidative/Nitrative Stress to Maximize Ferroptosis Therapy.

Ferroptosis is a novel type of nonapoptotic programmed cell death involving the accumulation of lipid peroxidation (LPO) to a lethal threshold. Herein, we propose tunable zeolitic imidazolate framework (ZIFs)-engineered biodegradable nanozymes for ferroptosis mediated by both reactive oxygen species (ROS) and nitrogen species (RNS). l-Arginine is utilized as an exogenous nitric oxide donor and loaded into hollow ZIFs@MnO2 artificial nanozymes, which are formed by etching ZIFs with potassium permanganate and simultaneously generating a MnO2 shell in situ. The constructed nanozymes with multienzyme-like activities including peroxidase, oxidase, and catalase can release satisfactory ROS and RNS through a cascade reaction, consequently promoting the accumulation of LPO. Furthermore, it can improve the efficiency of ferroptosis through a three-step strategy of glutathione (GSH) depletion; that is, the outer MnO2 layer consumes GSH under slightly acidic conditions and RNS downregulates SLC7A11 and glutathione reductase, thus directly inhibiting GSH biosynthesis and indirectly preventing GSH regeneration.

Nanozyme-Enhanced Electrochemical Biosensors: Mechanisms and Applications.

Nanozymes, as innovative materials, have demonstrated remarkable potential in the field of electrochemical biosensors. This article provides an overview of the mechanisms and extensive practical applications of nanozymes in electrochemical biosensors. First, the definition and characteristics of nanozymes are introduced, emphasizing their significant role in constructing efficient sensors. Subsequently, several common categories of nanozyme materials are delved into, including metal-based, carbon-based, metal-organic framework, and layered double hydroxide nanostructures, discussing their applications in electrochemical biosensors. Regarding their mechanisms, two key roles of nanozymes are particularly focused in electrochemical biosensors: selective enhancement and signal amplification, which crucially support the enhancement of sensor performance. In terms of practical applications, the widespread use of nanozyme-based electrochemical biosensors are showcased in various domains. From detecting biomolecules, pollutants, nucleic acids, proteins, to cells, providing robust means for high-sensitivity detection. Furthermore, insights into the future development of nanozyme-based electrochemical biosensors is provided, encompassing improvements and optimizations of nanozyme materials, innovative sensor design and integration, and the expansion of application fields through interdisciplinary collaboration. In conclusion, this article systematically presents the mechanisms and applications of nanozymes in electrochemical biosensors, offering valuable references and prospects for research and development in this field.

Engineering Copper-Containing Nanoparticles-Loaded Silicene Nanosheets with Triple Enzyme Mimicry Activities and Photothermal Effect for Promoting Bacteria-Infected Wound Healing.

Skin wounds accompanied by bacterial infections threaten human health, and conventional antibiotic treatments are ineffective for drug-resistant bacterial infections and chronically infected wounds. The development of non-antibiotic-dependent therapeutics is highly desired but remains a challenging issue. Recently, 2D silicene nanosheets with considerable biocompatibility, biodegradability, and photothermal-conversion performance have received increasing attention in biomedical fields. Herein, copper-containing nanoparticles-loaded silicene (Cu2.8O@silicene-BSA) nanosheets with triple enzyme mimicry catalytic (peroxidase, catalase, and oxidase-like) activities and photothermal function are rationally designed and fabricated for efficient bacterial elimination, angiogenesis promotion, and accelerated wound healing. Cu2.8O@silicene-BSA nanosheets display excellent antibacterial activity through synergistic effects of reactive oxygen species generated from multiple catalytic reactions, intrinsic bactericidal activity of released Cu2+ ions, and photothermal effects, achieving high antibacterial efficiencies on methicillin-resistant Staphylococcus aureus (MRSA) of 99.1 ± 0.7% in vitro and 97.2 ± 1.6% in vivo. In addition, Cu2.8O@silicene-BSA nanosheets exhibit high biocompatibility for promoting human umbilical vein endothelial cell (HUVEC) proliferation and angiogenic differentiation. In vivo experiments reveal that Cu2.8O@silicene-BSA nanosheets with synergistic photothermal/chemodynamic therapeutics effectively accelerate MRSA-infected wound healing by eliminating bacteria, alleviating inflammation, boosting collagen deposition, and promoting angiogenesis. This research presents a promising strategy to engineer photothermal-assisted nanozyme catalysis for bacteria-invaded wound healing.

All-in-One Zinc-Doped Prussian Blue Nanozyme for Efficient Capture, Separation, and Detection of Copper Ion (Cu2+ ) in Complicated Matrixes.

Copper is a vital micronutrient for lives and an important ingredient for bactericides and fungicides. Given its indispensable biological and agricultural roles, there is an urgent need to develop simple, affordable, and reliable methods for detecting copper in complicated matrixes, particularly in underdeveloped regions where costly standardized instruments and sample dilution procedures hinder progress. The findings that zinc-doped Prussian blue nanoparticle (ZnPB NP) exhibits exceptional efficiency in capturing and isolating copper ions, and accelerates the generation of dissolved oxygen in a solution of H2 O2 with remarkable sensitivity and selectivity, the signal of which displays a positive correlation with the copper level due to the copper-enhanced catalase-like activity of ZnPB NP, are presented. Consequently, the ZnPB NP serves as an all-in-one sensor for copper ion. The credibility of the method for copper assays in human urine and farmland soil is shown by comparing it to the standard instrumentation, yielding a coefficient of correlation (R2 = 0.9890), but the cost is dramatically reduced. This ZnPB nanozyme represents a first-generation probe for copper ion in complicated matrixes, laying the groundwork for the future development of a practical copper sensor that can be applied in resource-constrained environments.

Self-Cascade Ce-MOF-818 Nanozyme for Sequential Hydrolysis and Oxidation.

Mimicking efficient biocatalytic cascades using nanozymes has gained enormous attention in catalytic chemistry, but it remains challenging to develop a nanozyme-based cascade system to sequentially perform the desired reactions. Particularly, the integration of sequential hydrolysis and oxidation reactions into nanozyme-based cascade systems has not yet been achieved, despite their significant roles in various domains. Herein, a self-cascade Ce-MOF-818 nanozyme for sequential hydrolysis and oxidation reactions is developed. Ce-MOF-818 is the first Ce(IV)-based heterometallic metal-organic framework constructed through the coordination of Ce and Cu to distinct groups. It is successfully synthesized using an improved solvothermal method, overcoming the challenge posed by the significant difference in the binding speeds of Ce and Cu to ligands. With excellent organophosphate hydrolase-like (Km = 42.3 µM, Kcat = 0.0208 min-1 ) and catechol oxidase-like (Km = 2589 µM, Kcat = 1.25 s-1 ) activities attributed to its bimetallic active centers, Ce-MOF-818 serves as a promising self-cascade platform for sequential hydrolysis and oxidation. Notably, its catalytic efficiency surpasses that of physically mixed nanozymes by approximately fourfold, owning to the close integration of active sites. The developed hydrolysis-oxidation self-cascade nanozyme has promising potential applications in catalytic chemistry and provides valuable insights into the rational design of nanozyme-based cascade systems.

Kill Two Birds with One Stone: Dual-Metal MOF-Nanozyme-Decorated Hydrogels with ROS-Scavenging, Oxygen-Generating, and Antibacterial Abilities for Accelerating Infected Diabetic Wound Healing.

Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)-crosslinked chitosan (CS)-based hydrogels decorated with the biomimetic metal-organic framework (MOF)-nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP-CS (MCGC), are prepared. With catalase (CAT)-like activity, these dual-metal MOF-nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H2O2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management.

CuO Nanozymes Catalyze Cysteine and Glutathione Depletion Induced Ferroptosis and Cuproptosis for Synergistic Tumor Therapy.

The latest research identifies that cysteine (Cys) is one of the key factors in tumor proliferation, metastasis, and recurrence. The direct depletion of intracellular Cys shows a profound antitumor effect. However, using nanozymes to efficiently deplete Cys for tumor therapy has not yet attracted widespread attention. Here, a (3-carboxypropyl) triphenylphosphonium bromide-derived hyaluronic acid-modified copper oxide nanorods (denoted as MitCuOHA) are designed with cysteine oxidase-like, glutathione oxidase-like and peroxidase-like activities to realize Cys depletion and further induce cellular ferroptosis and cuproptosis for synergistic tumor therapy. MitCuOHA nanozymes can efficiently catalyze the depletion of Cys and glutathione (GSH), accompanied by the generation of H2O2 and the subsequent conversion into highly active hydroxyl radicals, thereby successfully inducing ferroptosis in cancer cells. Meanwhile, copper ions released by MitCuOHA under tumor microenvironment stimulation directly bind to lipoylated proteins of the tricarboxylic acid cycle, leading to the abnormal aggregation of lipoylated proteins and subsequent loss of iron-sulfur cluster proteins, which ultimately triggers proteotoxic stress and cell cuproptosis. Both in vitro and in vivo results show the drastically enhanced anticancer efficacy of Cys oxidation catalyzed by the MitCuOHA nanozymes, demonstrating the high feasibility of such catalytic Cys depletion-induced synergistic ferroptosis and cuproptosis therapeutic concept.

Self-Assembled Fe-Phenolic Acid Network Synergizes with Ferroptosis to Enhance Tumor Nanotherapy.

Natural polyphenolic compound rosmarinic acid (RA) has good antitumor activity. However, the distinctive tumor microenvironment, characterized by low pH and elevated levels of glutathione (GSH), enhances the tolerance of tumors to the singular anti-tumor treatment mode using RA, resulting in unsatisfactory therapeutic efficacy. Targeting nonapoptotic programmed cell death processes may provide another impetus to inhibit tumor growth. RA possesses the capability to coordinate with metal elements. To solve the effect restriction of the above single treatment mode, it is proposed to construct a self-assembled nanocomposite, Fe-RA. Under tumor microenvironment, Fe-RA nanocomposite exerts the characteristics of POD-like enzyme activity and depletion of GSH, producing a large amount of hydroxyl radical (·OH) while disrupting the antioxidant defense system of tumor cells. Moreover, due to the enhanced permeability and retention effect (EPR), Fe-RA can transport Fe2+ to a greater extent to tumor cells and increase intracellular iron content. Causing an imbalance in iron metabolism in tumor cells and promoting cell ferroptosis. The results of the synchrotron X-ray absorption spectroscopy (XAS) and high-resolution mass spectrometry (HRMS) prove the successful complexation of Fe-RA nanocomposite. Density functional theory (DFT) explains the efficient catalytic mechanism of its peroxide-like enzyme activity and the reaction principle with GSH.

A Versatile Nanozyme-Based NADH Circulating Oxidation Reactor for Tumor Therapy through Triple Cellular Metabolism Disruption.

Nanozyme-based metabolic regulation triggered by tumor-specific endogenous stimuli has emerged as a promising therapeutic strategy for tumors. The current efficacy, however, is constrained by the limited concentration of endogenous substrates and the metabolic plasticity of tumors. Consequently, the implementation of efficient metabolic regulation in tumor therapy is urgently needed. Herein, a versatile nanozyme-based nicotinamide adenine dinucleotide (NADH) circulating oxidation nanoreactor is reported. First, the synthesized cobalt-doped hollow carbon spheres (Co-HCS) possess NADH oxidase (NOX)-mimicking activity for the NADH oxidation to disrupt oxidative phosphorylation (OXPHOS) pathway of tumor cells. Second, the substrate-cycle manner of Co-HCS can be used for NADH circulating oxidation to overcome the limitation of substrate deficiency. Finally, 2-Deoxy-D-glucose (2-DG) and 6-aminonicotinamide (6-AN) are introduced to block glycolysis and pentose phosphate pathway (PPP), thus creating a versatile nanozyme-based NADH circulating oxidation nanoreactor (Co-HCS/D/A) for tumor therapy through triple cellular metabolism disruption. In vitro and in vivo results demonstrate that the designed nanoreactor not only enhances the catalytic efficiency but also disrupts the tumor metabolic homeostasis, leading to efficient therapy outcome. This study develops a novel NADH circulating oxidation nanoreactor for tumor therapy through triple cellular metabolism disruption, which addresses the limitations of current nanozyme-based metabolism regulation for tumor therapy.

Bioactive Metal-Organic Frameworks as a Distinctive Platform to Diagnosis and Treat Vascular Diseases.

Vascular diseases (VDs) pose the leading threat worldwide due to high morbidity and mortality. The detection of VDs is commonly dependent on individual signs, which limits the accuracy and timeliness of therapies, especially for asymptomatic patients in clinical management. Therefore, more effective early diagnosis and lesion-targeted treatments remain a pressing clinical need. Metal-organic frameworks (MOFs) are porous crystalline materials formed by the coordination of inorganic metal ions and organic ligands. Due to their unique high specific surface area, structural flexibility, and functional versatility, MOFs are recognized as highly promising candidates for diagnostic and therapeutic applications in the field of VDs. In this review, the potential of MOFs to act as biosensors, contrast agents, artificial nanozymes, and multifunctional therapeutic agents in the diagnosis and treatment of VDs from the clinical perspective, highlighting the integration between clinical methods with MOFs is generalized. At the same time, multidisciplinary cooperation from chemistry, physics, biology, and medicine to promote the substantial commercial transformation of MOFs in tackling VDs is called for.

Zinc-Based ROS Amplifiers Trigger Cancer Chemodynamic/Ion Interference Therapy Through Self-Cascade Catalysis.

Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) poses challenges. Herein, an H2O2 self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO2) (denoted as ZnO2@Pt). ZnO2 releases H2O2 in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H2O2 while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn2+ released from ZnO2 interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO2@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn2+ release, downregulating ATP and NAD+ levels. In vivo assessment of anticancer effects showed that ZnO2@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H2O2 self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.

Dual-Targeted Graphitic Cascade Nanozymes for Recognition and Treatment of Helicobacter pylori.

Helicobacter pylori (H. pylori) is the major etiological factor of a variety of gastric diseases. However, the treatment of H. pylori is challenged by the destruction of targeted drugs by gastric acid and pepsin. Herein, a dual-targeted cascade catalytic nanozyme PtCo@Graphene@Hemin-2(L-arginine) (PtCo@G@H2A) is designed for the treatment of H. pylori. The dual-targeting ability of PtCo@G@H2A is derived from directly targeting the receptor protein of H. pylori through hemin and responding to the acidic environment to cause charge reversal (protonation of L-arginine) to capture H. pylori, achieving efficient targeting effect. Compared with the single-targeting strategy relying on hemin, the dual-targeting strategy can greatly improve the targeting rate, achieving an increase of 850% targeting rate. At the concentration of NaHCO3 in intestinal fluid, the surface potential of PtCo@G@H2A can be quickly restored to avoid side effects. Meanwhile, PtCo@G@H2A has pH-responsive oxidase-like activity, which can generate nitric oxide (NO) through a cascade catalytic process that first generates reactive oxygen species (ROS) with oxygen, and further oxidizes L-arginine through ROS, realizing a superior acid-selective bactericidal effect. Overall, it proposes a promising strategy for the treatment of H. pylori that maintains high targeting and therapeutic effects in the environment of gastric acid and pepsin.