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Sepsis is a systemic inflammatory response syndrome with high morbidity and mortality mediated by infection‐caused oxidative stress. Early antioxidant intervention by removing excessively produced reactive oxygen and nitrogen species (RONS) is beneficial to the prevention and treatment of sepsis. However, traditional antioxidants have failed to improve patient outcomes due to insufficient activity and sustainability. Herein, by mimicking the electronic and structural characteristics of natural Cu‐only superoxide dismutase (SOD5), a single‐atom nanozyme (SAzyme) featuring coordinately unsaturated and atomically dispersed Cu‐N4 site was synthesized for effective sepsis treatment. The de novo‐designed Cu‐SAzyme exhibits a superior SOD‐like activity to efficiently eliminate O2•−, which is the source of multiple RONS, thus blocking the free radical chain reaction and subsequent inflammatory response in the early stage of sepsis. Moreover, the Cu‐SAzyme effectively harnessed systemic inflammation and multi‐organ injuries in sepsis animal models. These findings indicate that the developed Cu‐SAzyme possesses great potential as therapeutic nanomedicines for the treatment of sepsis. A SOD‐inspired copper single‐atom nanozyme (Cu‐SAzyme) was designed and synthesized by a two‐step scaffold‐adsorption method. The Cu‐SAzyme exhibits high catalytic activity to scavenge superoxide anion, the initiator of ROS, and thus effectively prevents the disease progression in septic animals.

Aptamer-based lateral flow analysis (Apt-LFAs) has promising applications in many fields. Nanozymes have demonstrated high potential in improving the performance of Apt-LFAs and have been increasingly utilized in recent studies. In this study, we developed a nanozyme-based Apt-LFA for the rapid and sensitive detection of kanamycin by using a novel dual-functionalized AuNPs@polyA-DNA/GpG-Cu[sup.2+] nanozyme as a nanoprobe. In the nanoprobe design, the polyA-cDNA strand can discriminate a kanamycin aptamer from the kanamycin/aptamer complex, and the GpG-Cu[sup.2+] complex can amplify the detection signal by catalyzing the chromogenic reaction. The nanozyme Apt-LFA can quantify kanamycin in the range of 1–250 ng/mL with an LOD of 0.08 ng/mL, which demonstrated a 4-fold sensitivity improvement and had a wider linear range than the conventional AuNP-based LFA. The Apt-LFA was successfully applied to the detection of kanamycin in honey with good recoveries. Our dual-functionalized AuNP nanoprobe is easily prepared and can be highly compatible with the conventional AuNP-DNA-based LFA platform; thus, it can be extended to the application of Apt-LFAs for other small molecules.

Endothelial senescence is a pivotal driver in the pathogenesis of atherosclerosis (AS), a process accompanied by metabolic reprogramming and increased lactate (LA) production. The accumulated LA stimulates reactive oxygen species (ROS) generation and the senescence-associated secretory phenotype, establishing a self-perpetuating inflammation-senescence feedback loop that accelerates disease progression. Therefore, depleting LA to inhibit cellular senescence represents a promising therapeutic strategy against AS. Here, we successfully fabricated a two-dimensional multi-enzyme-mimicking nanozyme (SnSe@TC MEM-nanozyme) by incorporating tannic acid-cerium (TA-Ce) frameworks onto the surface of SnSe nanozyme. Leveraging the anti-inflammatory/antioxidative properties of TA-Ce, the SnSe@TC MEM-nanozyme effectively alleviates oxidative stress and protects intracellular DNA from ROS damage. Endowed with lactate dehydrogenase-like activity, SnSe nanozyme converts LA to pyruvate, synergistically exerting anti-inflammatory and anti-senescence effects in endothelial cells while blocking endothelial-mesenchymal transition and restoring endothelial barrier function. In vitro and in vivo results confirm that the combination of anti-inflammatory/antioxidant therapy and modulation of LA levels effectively reduces plaque size and alleviates its pro-inflammatory environment. This study presents a pathology-targeted SnSe@TC MEM-nanozyme for treating AS, proposing a new paradigm of SnSe-based therapeutics for other age-related diseases. [Display omitted] •A distinct SnSe@TC MEM-nanozyme with LDH-like activity has been rationally designed and engineered.•The SnSe@TC MEM-nanozyme demonstrates superior inflammation-attenuating and anti-senescence efficacy.•The SnSe@TC MEM-nanozyme features high efficacy in regulating endothelial cell function.•The SnSe@TC MEM-nanozyme effectively curbs the progression of atherosclerosis.

The development is shown of rod-shaped manganese-based metal–organic frameworks (Mn-MOFs) as hot- and cold-adapted oxidase-like nanozymes, with strong magnetic properties. These Mn-MOFs enable highly sensitive detection of nitrite ions, utilizing both convenient colorimetric ratio analysis and a visual instrument-free-based approach compatible with smartphone-based detection. The Mn-MOF showed multi-functional activity, such as cold/hot-adapted and magnetic oxidase-like activity, catalyzing the oxidation of chromogenic substrates 3,3′,5,5′-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB). Mn-MOF shows high oxidase activity with  V max of 1.39 × 10 −8  M/s and K m of 0.068 mM for TMB oxidation. Nitrite ions further react with oxTMB to form a yellow color via diazotization resulting in the ratiometric change in absorbance (A 652 /A 461 ). The color ratio is also quantified through the naked eye and/or smartphone app by analyzing RGB values, providing a rapid, portable, and cost-effective method for on-site detection. When applying Mn-MOF for smartphone-based nitrite detection, it performs excellent detection, with a linear range of 5.0–55.0 µM and a limit of detection of 0.18 µM, superior to most of the oxidase nanozyme-based nitrite sensing platforms. The detection platforms develop sensing probes using a reusable nanozyme that enables highly sensitive and selective detection of nitrite, featuring a broad linear range and a low limit of detection. Graphical Abstract

Ascorbate peroxidase (APX) as a crucial antioxidant enzyme has drawn attentions for its utilization in preventing cells from oxidative stress responses by efficiently scavenging H2O2 in plants. For eliminating the specific inactivation of natural APXs and regulating the catalytic activity, single‐atom nanozymes are considered as promising classes of alternatives with similar active sites and maximal atomic utilization efficiency to natural APXs. Herein, graphitic carbon nitride (g‐C3N4) anchored with isolated single copper atoms (Cu SAs/CN) is designed as an efficient nanozyme with intrinsic APX mimetic behavior. The engineered Cu SAs/CN exhibits comparable specific activity and kinetics to the natural APXs. Based on the density functional theory (DFT), Cu‐N4 moieties in the active center of Cu SAs/CN are determined to exert such favorable APX catalytic performance, in which the electron transfer between Cu and coordinated N atoms facilitates the activation and cleavage of the adsorbed H2O2 molecules and results in fast kinetics. The constructed Cu SAs/CN nanozyme with superior APX‐like performance and high biocompatibility can be applied for effectively protecting the H2O2‐treated cells against oxidative injury in vitro. These findings report the single‐atom nanozymes as a successful paradigm for guiding nanozymes to implement APX mimetic performance for reactive oxygen species‐related biotherapeutic. Graphitic carbon nitride anchored with isolated single copper atoms (Cu SAs/CN) is firstly designed as an efficient nanozyme with intrinsic ascorbate peroxidase (APX) mimetic behavior. The engineered Cu SAs/CN exhibits comparable specific activity and kinetics to the natural APXs. Based on the superior APX‐like performance and high biocompatibility, Cu SAs/CN is applied for effectively protecting the H2O2‐treated cells against oxidative injury in vitro.

HighlightsThe characteristics of metal- and metal oxide-based nanozymes with diverse construction are dissertated.The intrinsic properties and catalytic mechanism of metal- and metal oxide-based nanozymes are discussed.The recent applications of metal- and metal oxide-based nanozymes in biological analysis, relieving inflammation, antibacterial, and cancer therapy are reviewed.Since the ferromagnetic (Fe3O4) nanoparticles were firstly reported to exert enzyme-like activity in 2007, extensive research progress in nanozymes has been made with deep investigation of diverse nanozymes and rapid development of related nanotechnologies. As promising alternatives for natural enzymes, nanozymes have broadened the way toward clinical medicine, food safety, environmental monitoring, and chemical production. The past decade has witnessed the rapid development of metal- and metal oxide-based nanozymes owing to their remarkable physicochemical properties in parallel with low cost, high stability, and easy storage. It is widely known that the deep study of catalytic activities and mechanism sheds significant influence on the applications of nanozymes. This review digs into the characteristics and intrinsic properties of metal- and metal oxide-based nanozymes, especially emphasizing their catalytic mechanism and recent applications in biological analysis, relieving inflammation, antibacterial, and cancer therapy. We also conclude the present challenges and provide insights into the future research of nanozymes constituted of metal and metal oxide nanomaterials.

The emergence of multi-drug resistant (MDR) pathogens is a major public health concern, posing a substantial global economic burden. Photothermal therapy (PTT) at mild temperature presents a promising alternative to traditional antibiotics due to its biological safety and ability to circumvent drug resistance. However, the efficacy of mild PTT is limited by bacterial thermotolerance. Herein, a nanocomposite, BP@Mn-NC, comprising black phosphorus nanosheets and a manganese-based nanozyme (Mn-NZ) is developed, which possesses both photothermal and catalytic properties. Mn-NZ imparts glucose oxidase- and peroxidase-like properties to BP@Mn-NC, generating reactive oxygen species (ROS) that induce lipid peroxidation and malondialdehyde accumulation across the bacterial cell membrane. This process disrupts unprotected respiratory chain complexes exposed on the bacterial cell membrane, leading to a reduction in the intracellular adenosine triphosphate (ATP) content. Consequently, mild PTT mediated by BP@Mn-NC effectively eliminates MDR infections by specifically impairing bacterial thermotolerance because of the dependence of bacterial heat shock proteins (HSPs) on ATP molecules for their proper functioning. This study paves the way for the development of a novel photothermal strategy to eradicate MDR pathogens, which targets bacterial HSPs through ROS-mediated inhibition of bacterial respiratory chain activity.

Oxidative stress induced by excess reactive oxygen species (ROS) is a primary pathogenic cause of acute kidney injury (AKI). Development of an effective antioxidation system to mitigate oxidative stress for alleviating AKI remains to be investigated. This study presents the synthesis of an ultra‐small Platinum (Pt) sulfur cluster (Pt5.65S), which functions as a pH‐activatable prefabricated nanozyme (pre‐nanozyme). This pre‐nanozyme releases hydrogen sulfide (H2S) and transforms into a nanozyme (Ptzyme) that mimics various antioxidant enzymes, including superoxide dismutase and catalase, within the inflammatory microenvironment. Notably, the Pt5.65S pre‐nanozyme exhibits an endo‐exogenous synergy‐enhanced antioxidant therapeutic mechanism. The Ptzyme reduces oxidative damage and inflammation, while the released H2S gas promotes proneurogenesis by activating Nrf2 and upregulating the expression of antioxidant molecules and enzymes. Consequently, the Pt5.65S pre‐nanozyme shows cytoprotective effects against ROS/reactive nitrogen species (RNS)‐mediated damage at remarkably low doses, significantly improving treatment efficacy in mouse models of kidney ischemia‐reperfusion injury and cisplatin‐induced AKI. Based on these findings, the H2S‐generating pre‐nanozyme may represent a promising therapeutic strategy for mitigating inflammatory diseases such as AKI and others. This study presents a novel ultrasmall Pt5.65S pre‐nanozyme that releases hydrogen sulfide and exhibits inducible antioxidant enzyme‐like activity in an acidic and inflammatory microenvironment for managing acute kidney injury by promoting Nrf2 activation and mitigating oxidative damage.

Nanozymes are nanomaterials with intrinsic natural enzyme-like catalytic properties. They have received extensive attention and have the potential to be an alternative to natural enzymes. Increasing the atom utilization rate of active centers in nanozymes has gradually become a concern of scientists. As the limit of designing nanozymes at the atomic level, single-atom nanozymes (SAzymes) have become the research frontier of the biomedical field recently because of their high atom utilization, well-defined active centers, and good natural enzyme mimicry. In this review, we first introduce the preparation of SAzymes through pyrolysis and defect engineering with regulated activity, then the characterization and surface modification methods of SAzymes are introduced. The possible influences of surface modification on the activity of SAzymes are discussed. Furthermore, we summarize the applications of SAzymes in the biomedical fields, especially in those of reactive oxygen species (ROS) scavenging and antibacterial. Finally, the challenges and opportunities of SAzymes are summarized and prospected.

Tumor microenvironment (TME)‐induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single‐atom catalysts (SACs) are a new type of nanozyme with incredible catalytic efficiency. Here, a single‐atom manganese (Mn)‐N/C nanozyme is constructed. Mn‐N/C catalyzes the conversion of cellular H2O2 to ∙OH through a Fenton‐like reaction and enables the sufficient generation of reactive oxygen species (ROS), which induces immunogenic cell death (ICD) of tumor cells and significantly promotes CD8+T anti‐tumor immunity. Moreover, RNA sequencing analysis reveals that Mn‐N/C treatment activates type I interferon (IFN) signaling, which is critical for Mn‐N/C‐mediated anti‐tumor immune response. Mechanistically, the release of cytosolic DNA and Mn2+ triggered by Mn‐N/C collectively activates the cGAS‐STING pathway, subsequently stimulating type I IFN induction. A highly efficient single‐atom nanozyme, Mn‐N/C, which enhances anti‐tumor immune response and exhibits synergistic therapeutic effects when combined with the anti‐PD‐L1 blockade, is proposed. This study reports a single‐atom manganese (Mn)‐N/C nanozyme with highly efficient peroxidase‐like activity. Mn‐N/C‐mediated catalytic reaction prompts the concurrent release of cytosolic DNA and Mn2+, which coordinately activate cGAS‐STING‐IFN signaling cascade, thereby robustly promoting CD8+T anti‐tumor immunity and suppressing tumor growth. Mn‐N/C exhibits synergistic effects when combined with anti‐PD‐L1 blockade, offering a promising avenue to improve the efficacy of immunotherapy.