Enzyme Mimetics Research Articles

Engineering Strain-Defects to Enhance Enzymatic Therapy and Induce Ferroptosis.

The effect of mimetic enzyme catalysis is often limited by insufficient activity and a single therapy is not sufficient to meet the application requirements. In this study, a multifunctional nanozyme, MMSR-pS-PEG, is designed and fabricated by modifying poly (ethylene glycol) grafted phosphorylated serine (pS-PEG) on mesoporous hollow MnMoOx spheres, followed by loading sorafenib (SRF) into the pores. Strain engineering-induced oxygen defects endow the nanozyme with enhanced dual-enzymatic activity to mimic catalase and oxidase-like activities, which catalyze the conversion of endogenous H2O2 into oxygen and subsequently into superoxide ions in the acidic tumor microenvironment. Moreover, as an n-type semiconductor, MnMoOx generates reactive oxygen species by separating electrons and holes upon ultrasonic irradiation and simultaneously deplete glutathione by holes, thereby further augmenting its catalytic effect. As a ferroptosis inducer, SRF restrains the system xc - and indirectly inhibits glutathione synthesis, synergistically interacting with the nanozyme to stimulate ferroptosis by promoting lipid peroxidation and accumulation and the downregulation of glutathione peroxidase 4. These results provide valuable insights into the design of enzymatic therapy with high performance and highlight a promising approach for the synergism of ferroptosis and enzymatic tumor therapy.

Nickel-doped cuprous oxide nanocauliflowers with specific peroxidase-like activity for sensitive detection of hydrogen peroxide and uric acid

Copper-based nanomaterials have the properties of mimetic enzymes and can be used as excellent candidates for colorimetric sensing due to their environmental friendliness, low cost, and high abundance. In this paper, Ni-doped Cu2O nano cauliflower (Ni-Cu2O) was synthesized for the first time and applied to the detection of H2O2 and uric acid (UA) in human serum and urine. It was found that the proportion of Ni incorporation controls the morphology and the catalytic effect of Ni-Cu2O. The catalytic mechanism was studied by X-ray photoelectron spectroscopy, free radical capture experiments, photoluminescence spectroscopy, and steady-state kinetic analysis, which verified the redox reactions involving electron transfer and active substances. The results showed that Ni-Cu2O could catalyze the formation of reactive oxygen species (•OH, O2•−, 1O2, h+) from H2O2, which could oxidize 3,3′, 5,5′-tetramethylbenzidine (TMB) to oxTMB, and the color changed from colorless to blue. The Michaelis-Menten constant (Km) and the maximum initial velocity (Vmax) of Ni-Cu2O were 1.8 mM and 15.2×10−8 M/s, respectively. Based on the excellent peroxidase-like (POD) activity of Ni-Cu2O, a colorimetric sensing platform combined with TMB was proposed to sensitively detect H2O2 and UA in a wide range, and the detection limits were as low as 0.17 μM and 0.22 μM, respectively. This study creates a platform for using the Cu-based cauliflowers as a biosensor to detect UA in the medical and biomedicine fields.

Sensitive detection of Vibrio parahaemolyticus via a dual-recognition colorimetric biosensor comprising Cefe-PEG-MNPs and apt-Fe@PDA

Highly accurate and sensitive detection of Vibrio parahaemolyticus is crucial for ensuring seafood safety and preventing the transmission of foodborne diseases. Herein, a dual-recognition strategy-driven colorimetric biosensor for the detection of V. parahaemolyticus was developed. This biosensor was based on the use of PEG-mediated cefepime-functionalized magnetic nanoparticles (Cefe-PEG-MNPs) and aptamer-modified Fe-doped polydopamine (Fe@PDA) nanozymes. The magnetic platform Cefe-PEG-MNPs was introduced to enhance the enrichment efficiency of V. parahaemolyticus, achieving a capture efficiency exceeding 90%. The Fe@PDA nanozyme exhibited notable peroxidase mimetic enzyme activity. The colorimetric biosensor developed for V. parahaemolyticus detection demonstrated good sensitivity, with a detection range spanning from 2.1 × 101 to 2.1 × 106 CFU/mL, and a limit of detection of 21 CFU/mL. Moreover, the biosensor demonstrated remarkable specificity, achieving good recovery rates from 95.80% to 103.80% in Penaeus vannamei with a relative standard deviation of less than 1.38%. The newly developed colorimetric biosensor offers a remarkable opportunity for the accurate and sensitive detection of V. parahaemolyticus in seafood.

A molecularly imprinted electrochemiluminescence sensor based on mimic enzyme ZIF-90 and MnO2/g-C3N4 magnetic particles for detection of methidathion.

Methidathion (MTDT), a common organophosphorus pesticide with high insecticidal activity, is widely used for pest control. However, the misuse of MTDT leads to widespread residues and endangers human health. Therefore, it is crucial to develop a simple and highly sensitive method for the detection of MTDT residues. Herein, ZIF-90/MnO2/g-C3N4/Fe3O4 composite particles were synthesized: The MnO2 nanosheets could absorb the energy of the excited g-C3N4 to quench the ECL of g-C3N4 while ZIF-90 acted as a mimetic enzyme to catalyze the formation of thiocholine from MTDT. The thiocholine caused the reduction of MnO2 to Mn2+, restoring the ECL signal of g-C3N4. Combined with molecular imprinting technique, an electrochemiluminescence sensor was constructed for the determination of MTDT. The determination range was 1.00 × 10-9 ~ 7.00 × 10-7g/L, and the detection limit was 6.58 × 10-10g/L. Structurally similar organophosphorus pesticides showed no cross-reactivity. The method has high sensitivity and specificity, and has been successfully applied to the determination of MTDT residue in fruits with recoveries in the range 93.75% ~ 102.37%.

Bimetallic metal organic frameworks-based nanozyme for colorimetry/fluorescence dual-mode uremic toxin detection

Chronic kidney disease (CKD) can greatly increase the mortality risk for clinical patients, with a major challenge being the accurate detection of uremic toxins. Metal organic frameworks (MOFs)-based colorimetry/fluorescence dual-mode probe have shown great potential for bio-detection. However, one of the challenges for MOFs-based nanoprobe is to effectively improve the activity of mimetic enzymes for colorimetric assays while maintaining their outstanding luminescence response for fluorescence sensing. Here, we developed a novel bimetallic Zr/Ce-MOFs, which possesses high catalytic activity and excellent luminescence properties for dual-mode sensing of uremic toxins. The co-existence of Ce and Zr in the MOFs improves the catalytic activity for colorimetric detection of phosphate ions (one type of uremic toxins) and the strong coordinate covalent interaction between phosphate ions and Zr/Ce leads to a significant fluorescence enhancement of the MOFs. Furthermore, we achieved high sensitivity phosphate ions analysis in serum samples. This strategy provides an easy and reliable platform for the detection of uremic toxins in complicated physiological environment.

Portable multimodal platform with carbon nano-onions as colorimetric and fluorescent signal output for trypsin detection

Multimodal biosensors with independent signaling pathways can self-calibrate and improve the reliability of disease biomarker detection. Herein, a colorimetric-fluorescent dual-mode paper-based biosensor with PAN/Fe(III)–CNOs (FPCs) as core components has been developed, which information is recognized by smartphone and naked eye. Using 1-(2-pyridylazo)-2-naphthol (PAN) as a mediator, Fe(III) is enriched on the surface of carbon nano-onions (CNOs), endowing FPCs with excellent mimetic enzyme activity and photothermal conversion ability, which allows it to output amplified colorimetric signals under laser irradiation. In addition, the complexation of PAN with Fe(III) broadens its absorption spectrum, which makes FPCs more suitable to be energy acceptors to quench fluorescence of polymer dots (Pdots), resulting in the changes of output fluorescent signal. Based on the above design, a portable colorimetric-fluorescent dual-mode biosensor is proposed for trypsin detection with Pdots as fluorescence sources and FPCs as fluorescence quenchers and nanoenzymes. This work provides a convenient way for constructing portable visual multimodal biosensors, which is expected to applied in various disease diagnosis.

Bimetallic Single-Atom Nanozyme-Based Electrochemical-Photothermal Dual-Function Portable Immunoassay with Smartphone Imaging.

Rapid and accurate detection of human epidermal growth factor receptor 2 (HER2) is crucial for the early diagnosis and prognosis of breast cancer. In this study, we reported an iron-manganese ion N-doped carbon single-atom catalyst (FeMn-NCetch/SAC) bimetallic peroxidase mimetic enzyme with abundant active sites etched by H2O2 and further demonstrated unique advantages of single-atom bimetallic nanozymes in generating hydroxyl radicals by density functional theory (DFT) calculations. As a proof of concept, a portable device-dependent electrochemical-photothermal bifunctional immunoassay detection platform was designed to achieve reliable detection of HER2. In the enzyme-linked reaction, H2O2 was generated by substrate catalysis via secondary antibody-labeled glucose oxidase (GOx), while FeMn-NCetch/SAC nanozymes catalyzed the decomposition of H2O2 to form OH*, which catalyzed the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) to ox-TMB. The ox-TMB generation was converted from the colorimetric signals to electrical and photothermal signals by applied potential and laser irradiation, which could be employed for the quantitative detection of HER2. With the help of this bifunctional detection technology, HER2 was accurately detected in two ways: photothermally, with a linear scope of 0.01 to 2.0 ng mL-1 and a limit of detection (LOD) of 7.5 pg mL-1, and electrochemically, with a linear scope of 0.01 to 10 ng mL-1 at an LOD of 3.9 pg mL-1. By successfully avoiding environmental impacts, the bifunctional-based immunosensing strategy offers strong support for accurate clinical detection.

Integrating a Copper-Histidine Brace in a Mimetic Nanozyme Streamlines the Tyrosinase Recognition Moiety to Achieve Chiral Differentiation.

Designing artificial mimetic enzymes with high activity/selectivity to replace chiral bioenzymes is of great interest in the development of chiral materials consisting of molecules, enantiomers, that exist in two forms as mirror images of one another but cannot be superimposed. In this study, the chiral catalytic structural unit was streamlined from tyrosinase to integrate a mimetic nanozyme. The chiral amino acid l-histidine, as the chiral binding/recognition site, and the active metal site Cu were coupled (Cu@l-His) to create a copper-histidine brace with enantioselective catalytic ability to tyrosinol enantiomers. Results of kinetic parameters and activation energies confirmed the excellent peroxidase-like activity with a preference of Cu@l-His to l-tyrosinol. Such a preference could be attributed to the structurally oriented copper-histidine brace with a stronger affinity and catalytic activity to l-tyrosinol. By accurately evaluating chiral recognition units derived from bioenzymes, stable and superior chiral mimetic nanoenzymes could be constructed in a more straightforward and simplified manner, and they could also be extended to the reconstruction of diverse chiral enzymes.

Enhancing Therapeutic Efficacy of Cerium Oxide Nanoparticles (CNP) Conjugated with S-Nitroso-N-acetyl Penicillamine for Multifunctional Biomedical Applications

Nanoparticles are extensively used because their small size, unique orientation, and distinct physical properties can significantly modify the behavior of the materials they interact with. Cerium oxide nanoparticles (CNP) also known as nanoceria are gaining popularity in a multitude of sectors, including Biomedical science as drug delivery, therapeutics, and enzyme mimetics. Nanoceria are preferred over typical antioxidants or enzymes because they can scavenge numerous types of free radicals. Studies such as In vitro and in vivo methods have shown that nanoceria may be employed as a carrier for targeted medication and gene delivery. Nanoceria works as an antioxidant therapeutics in healthy cells by scavenging ROS (at physiological pH) free radicals. Furthermore, S-Nitroso-N-acetyl penicillamine (SNAP), a nitroso thiol derivative, releases nitric oxide (NO) under physiological conditions. This makes SNAP a valuable tool for researching the pharmacological and physiological effects of NO. The conjugation of CNP and SNAP along with bacterial cellulose enhances its antimicrobial, SOD, and antidiabetic activities. CNP was synthesized using the Wet chemistry method and optimized using a UV/Vis Spectrophotometer. Further, the conjugate solution was characterized by UV-Vis (i.e., within the range of 230-280 nm) and SEM shows a perfect conjugate solution by its morphology and elements. The anti-microbial activity was administered, and a moderate zone was observed. The zone of inhibition activity was shown 4 mm against gram-negative bacteria and 7 mm against gram-positive bacteria. The conjugate solution examined cellular viability of approximately 50.6 % in HACAT cells which shows less toxicity. These observations concluded that the procedure for nanoparticle synthesis is advantageous and synthesized nanomaterial was found to be highly Antioxidative.

Cu(II)-chelated ovalbumin mimicking the active centre of superoxide dismutase: Structure, antioxidant and antibacterial properties for food preservation application

Enzymatic browning and microbial contamination of food threaten food sensory and safety. With the development of green and healthy concepts, there is a greater need for efficient, low-carbon antioxidant and antimicrobial strategies. In this study, we designed a nano-enzyme with antioxidant activities and biocompatibility. By mimicking the active center of the natural SOD enzyme, copper (Cu) and ovalbumin (OVA) were self-assembled to form Cu-nano-polymerised sheet (Cu-NPS), in which OVA as a scaffold carries cofactors to create the active sites, making the nanoenzymes compatible with the antioxidant activity and antimicrobial properties of Cu, and at the same time possessing good stability and biocompatibility. These properties enable Cu-NPS to have a broader application range, for removing reactive oxygen species (ROS) and broad-spectrum sterilization. Subsequently, Cu-NPS was doped into carrageenan (Carr) to form a nanocomposite film, effectively inhibiting enzymatic browning and microbial contamination. In this work, protein-based mimetic enzymes as artificial nanoenzymes have advantages over natural enzymes, and the Cu-NPS with simple synthesis, high stability, and diverse properties, provides new ideas for the design of functional materials.

ZIF-8@Pt Nanozyme Used for Scavenging Reactive Oxygen Species in the Treatment of Rheumatoid Arthritis

To formulate a ZIF-8 nano mimetic enzyme conjugated with platinum metal (ZIF-8@Pt) that can scavenge reactive oxygen species (ROS) and to explore its potential applications in the treatment of rheumatoid arthritis (RA). The ZIF-8@Pt nanozyme was created by in situ reduction. Characterization of the nanozyme was then performed and its ability to mimic enzymes was investigated. Cell experiments were conducted using RAW264.7 cells, which were divided into three groups, including the untreated group (UT), the positive control group receiving lipopolysaccharide (LPS), which was designated as the LPS group, and the ZIF-8@Pt group receiving ZIF-8@Pt and LPS treatment. The cell experiments were conducted to evaluate the anti-inflammatory properties of ZIF-8@Pt through scavenging intracellular ROS. On the other hand, a collagen-induced arthritis (CIA) model was induced in rats. Similar to the group designations in the cell experiments, the rats were assigned to three groups, including a healthy control group (the UT group), a positive control group receiving a local injection of PBS solution in the knee joint, which was referred to as the control group, and a treatment group receiving a local injection of ZIF-8@Pt solution in the knee joint, which was referred to as the ZIF-8@Pt group. General evaluation, imaging observation, assessment of inflammatory factors, and pathological evaluation were performed to assess the therapeutic efficacy of ZIF-8@Pt against RA. The in vitro experiment revealed significant difference in the levels of intracellular ROS and LPS-induced M1-type macrophage polarization between the LPS group and the ZIF-8@Pt group (P<0.05). The in vivo experiment showed that significant difference in the levels of inflammatory factors, including interleukin-1β (IL-1β), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and arginase-1 (Arg-1) in the knee joints of the CIA rats between the LPS group and the ZIF-8@Pt group (P<0.05). Comparing the findings for the ZIF-8@Pt group and the control group, pathology assessment revealed that ZIF-8@Pt reduced local hypoxia and suppressed osteoclastic activity, neovascularization, and M1-type macrophage polarization (P<0.05). The ZIF-8@Pt enzyme mimetic inhibits macrophage inflammatory polarization by ROS scavenging, thereby improving inflammation in RA. Furthermore, the ZIF-8@Pt nanozyme improves the hypoxic environment and inhibits angiogenesis and bone destruction, demonstrating promising therapeutic efficacy for RA.

Biomass carbon quantum dots: Mimicking peroxidase-like activity and sensitive fluorometric and colorimetric detection of dopamine hydrochloride in meat products

Dopamine (DH), as a kind of "lean meat powder", is easily accumulated in animal tissues and further endangers the health of consumers. As a result, developing a quick, sensitive, and cost-effective approach for detecting DH concentration is critical to food safety. In this paper, fluorescent carbon quantum dot (CQDs) peroxidase mimetic enzymes with remarkable stability and high catalytic efficiency were produced utilizing a green synthesis technique from three types of food waste: corncob, sunflower seed husk, and grape seed. Then a colorimetric/fluorescent dual-mode sensor based on fluorescent CQDs was developed for the visual detection of dopamine hydrochloride in pork through changing the fluorescence brightness and color caused by its catalysis. The fluorescent CQDs generated from the three wastes were characterized, and the ones based on corncob performed the best as mimicked enzymes. Therefore, corncob fluorescent CQDs (CFCD) were used for the detection of DH. Under the optimal conditions, the linear range of DH measured by the fluorescent technique was 0.001–0.6 mmol/L (R2 = 0.9947), with a detection limit of 7.86 nmol/L. The linear range of DH measured by the colorimetric technique was 0.001–0.7 mmol/L (R2 = 0.9952), with a detection limit of 0.93 μmol/L. And with its high sensitivity and selectivity, it was successfully applied to the detection of DH in real samples. The developed CFCD concept may provide a novel method for the detection of DH. This comprehensive strategy promotes the high-efficiency conversion of biomass into CQDs and provides a theoretical basis for exploring the treatment of biomass waste.

Rapid, portable, and sensitive detection of CaMV35S by RPA-CRISPR/Cas12a-G4 colorimetric assays with high accuracy deep learning object recognition and classification

Fast, sensitive, and portable detection of genetic modification contributes to agricultural security and food safety. Here, we developed RPA-CRISPR/Cas12a-G-quadruplex colorimetric assays that can combine with intelligent recognition by deep learning algorithms to achieve sensitive, rapid, and portable detection of the CaMV35S promoter. When the crRNA-Cas12a complex recognizes the RPA amplification product, Cas12 cleaves the G-quadruplex, causing the G4-Hemin complex to lose its peroxide mimetic enzyme function and be unable to catalyze the conversion of ABTS2− to ABTS, allowing CaMV35S concentration to be determined based on ABTS absorbance. By utilizing the RPA-CRISPR/Cas12a-G4 assay, we achieved a CaMV35S limit of detection down to 10 aM and a 0.01 % genetic modification sample in 45 min. Deep learning algorithms are designed for highly accurate classification of color results. Yolov5 objective finding and Resnet classification algorithms have been trained to identify trace (0.01 %) CaMV35S more accurately than naked eye colorimetry. We also coupled deep learning algorithms with a smartphone app to achieve portable and rapid photo identification. Overall, our findings enable low cost ($0.43), high accuracy, and intelligent detection of the CaMV35S promoter.

Simultaneous sterilization and biosensing of pathogenic bacteria via copper phthalocyanine-based COF embedded with Cu-N4 single atomic sites and silver nanoparticles

The efficient inactivation and sensitive detection of waste water and food stuffs polluted by pathogenic bacteria are vital for ensuring food safety and protecting people’s healthy. Herein, a 2D copper phthalocyanine-based covalent-organic framework (COF) embraced with Cu-N4 single atomic sites and silver nanoparticles (denoted as CuPc-Dha-COF@AgNPs) was employed as a bifunctional bioplatform for the efficient sterilization via the multi-modal antibacterial mechanism and the sensitive detection of pathogenic bacteria via the photocatalytic oxidization of glutathione (GSH) using a photoelectrochemical (PEC) technique. Given the superior photothermal conversion efficiency, the high production efficiency of reactive oxygen species, the enhanced H2O2 self-supplying capability, and the controlled release of Ag+ ions under near-infrared light irradiation (808 nm and 1.0 W cm−2), 100 % bacteria were eliminated by CuPc-Dha-COF@AgNPs (200 μg mL−1) at 24 h. Furthermore, the CuPc-Dha-COF@AgNPs-based PEC biosensing platform exhibited highly selective determination ability toward GSH because of its superior mimetic enzyme performance caused by Cu-N4 single atomic sites, narrow bandgap, wide photoabsorption performance, and high separation of photoinduced electrons and holes. It thus showed an ultralow detection limit of 99 fM toward GSH within wide range from 1.0 pM to 1.0 nM, as well as high selectivity, good stability and reproducibility, and promising practicality. This work provides a new strategy for the sterilization and sensitive detection of pathogenic bacteria, simultaneously implementing and monitoring measures for the water system and food safety.

A novel Fe3O4@Pt synthetized via a self-assembly strategy as efficient Fenton-like@mimetic enzyme catalyst for degradation of tetracyclines in food processing wastewater

The self-assembly approach has successfully been used to generate Fe3O4@Pt, a material that can mimic peroxidase. The material was created by modifying the surface of Fe3O4 nanoparticles (Fe3O4 NPs) with -NH2 functional groups using 3-Aminopropyltriethoxysilane (APTES), and then using the coordination between platinum ions and -NH2 on the surface of magnetic particles to reduce platinum ions to the surface of magnetic particles under ultrasonic conditions to produce Fe3O4@Pt composite nanoparticles. The Fe3O4@Pt core-shell composite material not only has the inert metal Pt to protect Fe3O4 to improve the stability of Fe3O4 in the biological matrix, but also has the high catalytic activity of Fe3O4 and Pt. The catalysts were characterized, and the findings revealed that they were non-homogeneous Fenton catalysts with high dispersion, uniform particle size, and a large specific surface area. Since a large number of free radicals generated during the catalysis of Fe3O4@Pt mimic enzyme can trigger the Fenton reaction, tetracycline (TC) and oxytetracycline (OTC) were chosen as target substances, and a system for the combined degradation of tetracyclines pollutants by mimic enzyme and Fenton reaction was established, and the catalytic mechanism of this system has been investigated. The findings indicate that by using a concentration of 0.25 mol/L of H2O2, a catalyst amount of 1.5 g/L, a reaction time of 50 min, and a reaction temperature of 50°C, the degradation rate of TC and OTC can exceed 97 %, following first-order degradation kinetics. Under ideal conditions, over 95 % of each tetracyclines was degraded in the simulated food processing wastewater, effectively achieving tetracyclines degradation in the actual wastewater. In addition, the reusability of the recovered Fe3O4@Pt mimetic enzyme was investigated. The findings indicated that the Fe3O4@Pt mimetic enzyme has exceptional activity, stability, and reproducibility. The combination of the Fenton reaction with the Fe3O4@Pt mimetic enzyme can expedite the degradation of tetracyclines, offering a novel approach for eliminating recalcitrant contaminants in wastewater.

Metal-ligand cross-link strategy engineered iron-doped dopamine-based superstructure as peroxidase-like nanozymes for detection of glucose.

Nanozymes are nanomaterials with mimetic enzyme properties and the related research has attracted much attention. It is of great value to develop methods to construct nanozymes and to study their application in bioanalysis. Herein, the metal-ligand cross-linking strategy was developed to fabricate superstructure nanozymes. This strategy takes advantage of beingeasy to operate, adjustable, cheap, and universal. The fabricated superstructure nanozymes possess efficient peroxidase-like catalytic activity. The enzyme reaction kinetic tests demonstrated that for TMB and H2O2, the Km is 0.229 and 1.308mM, respectively. Furthermore, these superstructure nanozymes are applied to highly efficient and sensitive detection of glucose. The linear range for detecting glucose is 20-2000μM, and the limit of detection is 17.5μM. Furthermore, mechanistic research illustrated that this integrated system oxidizes glucose to produce hydrogen peroxide and further catalyzes the production of ·OH and O2·-, which results in a chromogenic reaction of oxidized TMB for the detection of glucose. This work could not only contribute to the development of efficient nanozymes but also inspire research in the highly sensitive detection of other biomarkers.

Biodegradable pyroptosis inducer with multienzyme-mimic activity kicks up reactive oxygen species storm for sensitizing immunotherapy

Triggering pyroptosis is a major new weathervane for activating tumor immune response. However, biodegradable pyroptosis inducers for the safe and efficient treatment of tumors are still scarce. Herein, a novel tumor microenvironment (TME)-responsive activation nanoneedle for pyroptosis induction, copper-tannic acid (CuTA), was synthesized and combined with the sonosensitizer Chlorin e6 (Ce6) to form a pyroptosis amplifier (CuTA-Ce6) for dual activation and amplification of pyroptosis by exogenous ultrasound (US) and TME. It was demonstrated that Ce6-triggered sonodynamic therapy (SDT) further enhanced the cellular pyroptosis caused by CuTA, activating the body to develop a powerful anti-tumor immune response. Concretely, CuTA nanoneedles with quadruple mimetic enzyme activity could be activated to an “active” state in the TME, destroying the antioxidant defense system of the tumor cells through self-destructive degradation, breaking the “immunosilent” TME, and thus realizing the pyroptosis-mediated immunotherapy with fewer systemic side effects. Considering the outstanding oxygen-producing capacity of CuTA and the distinctive advantages of US, the sonosensitizer Ce6 was attached to CuTA via an amide reaction, which further amplified the pyroptosis and sensitized pyroptosis-induced immunotherapy with the two-pronged strategy of CuTA enzyme-catalyzed cascade and US-driven SDT pathway to generate a “reactive oxygen species (ROS) storm”. Conclusively, this work provided a representative paradigm for achieving safe, reliable and efficient pyroptosis, which was further enhanced by SDT for more robust immunotherapy.

Highly Selective Isomerization of Glucose to Fructose through a Biphasic and Recyclable Mimetic Enzyme Catalyst

AbstractDeveloping a biphasic catalyst is of great significance for improving reaction efficiency and its industrial application. Herein a novel biphasic catalyst containing three functional groups of chlorophenol, amino and carboxyl was synthesized and used as mimic glucose isomerase to catalyze the isomerization. The mimic enzyme exhibited excellent catalytic performance for isomerization of glucose to fructose under mild conditions. Temperature and pH of solution showed significant influence on the conversion of glucose and the selectivity of fructose. The yield and selectivity of fructose reached 32.4 % and 91.0 % after reacting 2 h, respectively, at pH 9.5 and 90 °C. The solubility of the catalyst exhibited dual sensitivity to both pH and temperature. The catalyst was in a soluble state during the reaction process and could be precipitated by reducing the pH and temperature of the reaction system. The catalyst could be reused and still maintained good catalytic activity after five consecutive cycles.

An artificial protein modulator reprogramming neuronal protein functions

Reversible protein phosphorylation, regulated by protein phosphatases, fine-tunes target protein function and plays a vital role in biological processes. Dysregulation of this process leads to aberrant post-translational modifications (PTMs) and contributes to disease development. Despite the widespread use of artificial catalysts as enzyme mimetics, their direct modulation of proteins remains largely unexplored. To address this gap and enable the reversal of aberrant PTMs for disease therapy, we present the development of artificial protein modulators (APROMs). Through atomic-level engineering of heterogeneous catalysts with asymmetric catalytic centers, these modulators bear structural similarities to protein phosphatases and exhibit remarkable ability to destabilize the bridging μ3-hydroxide. This activation of catalytic centers enables spontaneous hydrolysis of phospho-substrates, providing precise control over PTMs. Notably, APROMs, with protein phosphatase-like characteristics, catalytically reprogram the biological function of α-synuclein by directly hydrolyzing hyperphosphorylated α-synuclein. Consequently, synaptic function is reinforced in Parkinson’s disease. Our findings offer a promising avenue for reprogramming protein function through de novo PTMs strategy.

Fabrication of a dual mimetic enzyme sensor based on gold nanoparticles modified with Cu(II)-coordinated methanobactin for gallic acid detection

Fabrication of a dual mimetic enzyme sensor based on gold nanoparticles modified with Cu(II)-coordinated methanobactin for gallic acid detection