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In this work, a self-powered microsensor platform based on enzyme biofuel cells (EBFCs) was developed for intelligent monitoring of disease markers miRNA-451. The cascade catalysis system constructed by using the strategy of enzyme-like ZIF-8 nanocapsule incorporation with biological enzymes, which could simultaneously take into account the specificity of biological enzymes and the high activity of nano-enzymes, significantly promoted the electron transfer between glucose and the bio-anode surface, and improved the sensitivity and stability of the sensing system. Meanwhile, the target-triggered hybridization chain reaction (HCR) amplification strategy to achieve exponential signal amplification based on accurate recognition, and jointly improve the detection sensitivity. As expected, the micro-sensor platform has a wide linear range of 0.5-1.0 fmol/L with a low limit of detection (LOD) of 0.13 fmol/L (S/N = 3) and exhibits excellent selectivity, reproducibility and stability in interference assays under optimal detection conditions. The designed self-powered system is simple to construct, easy to transport and the data transmission mode is intelligent and controllable, which is expected to be used in basic biochemical research, clinical diagnosis and environmental monitoring., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Developing nanozymes for cancer therapy has attracted great attention from researchers. However, enzymes-loaded magnetic particles triggered by both a low-frequency vibrating magnetic field (VMF) and laser for inhibiting tumor growth have never been reported. Herein, we developed a magnetic nanozyme with 3D flower-like nanostructures for cancer therapy. Specifically, the flower-like nanozymes exposed to a VMF could efficiently damage the mitochondrial membrane and cell structure, and inhibit tumor growth through magneto-mechanical force. In parallel, magnetic nanozymes in a weak acid environment containing glucose could generate abundant hydrogen peroxide through glucose oxidase-catalyzed oxidation of glucose, and further significantly promote the Fenton reaction. Interestingly, both glucose oxidase- and Fenton-based catalytic reactions were significantly promoted by the VMF exposure. Flower-like magnetic nanospheres upon a near-infrared laser irradiation could also damage cancer cells and tumor tissues through photothermal effect. The cell-killing efficiency of magnetic nanozymes triggered by the VMF or laser significantly increased in comparison with that of nanozymes without exposures. Mouse tumors grown after injection with magnetic nanozymes was inhibited in a significant way or the tumors disappeared after exposure to a VMF and laser due to the synergistic effect of four major stimuli, viz., magneto-mechanical force, photothermal conversion, improved Fenton reaction, and intratumoral glucose consumption-based starvation effect. This is a great platform that may be suitable for treating many solid tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bimetallic nanozymes exhibited multi-enzyme activities, but glutathione (GSH) overexpression and weak catalytic capability restricted their catalytic therapeutic performance. Thus, this study developed a smart nanozyme (AuPt@MnO 2 ) with a core-shell structure by coating manganese dioxide (MnO 2 ) on the gold-platinum (AuPt) nanozyme (AuPt@MnO 2 ) surface to enhance catalytic therapy. In this nanozyme, AuPt possessed triple-enzyme activities, i.e., catalase, peroxidase, and glucose oxidase, which greatly improved oxygen, hydroxyl radicals (·OH), and hydrogen peroxide generation, due to cyclic reactions. Moreover, GSH consumption degraded the MnO 2 shell, which then enhanced ·OH generation of Mn 2+ . More importantly, the near-infrared-II (NIR-II) photothermal performance of AuPt@MnO 2 with a high conversion efficiency of 38.7 % further promoted multi-enzyme activities and enhanced catalytic therapy. Moreover, combining NIR-II photothermal therapy and enhancing catalytic therapy decreased the cell viability to 10.8 %, and thereby, the tumors were cleared. Thus, the AuPt@MnO 2 smart nanoplatform developed in this study exhibited NIR-II photothermal-promoted multi-enzyme activities and excellent antitumor efficacy, which will be promising for enhancing catalytic therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Conventionally, the optimization of glucose biosensors is achieved by varying the concentrations of the individual reagents used to immobilize the enzyme. In this work, the effect and interaction between glucose oxidase enzyme (GOx), ferrocene methanol (Fc), and multi-walled carbon nanotubes (MWCNTs) at different concentrations were investigated by a design of experiments (DoE). For this analysis, a factorial design with three factors and two levels each was used with the software RStudio for statistical analysis. The data were obtained by electrochemical experiments on the immobilization of GOx-Fc/MWCNT at different concentrations. The results showed that the factorial DoE method was confirmed by the non-normality of the residuals and the outliers of the experiment. When examining the effects of the variables, analyzing the half-normal distribution and the effects and contrasts for GOx-Fc/MWCNT, the factors that showed the greatest influence on the electrochemical response were GOx, MWCNT, Fc, and MWCNT:Fc, and there is a high correlation between the factors GOx, MWCNT, Fc, and MWCNT:Fc, as shown by the analysis of homoscedasticity and multicollinearity. With these statistical analyses and experimental designs, it was possible to find the optimal conditions for different factors: 10 mM mL -1 GOx, 2 mg mL -1 Fc, and 15 mg mL -1 MWCNT show a greater amperometric response in the glucose oxidation. This work contributes to advancing enzyme immobilization strategies for glucose biosensor applications. Systematic investigation of DoE leads to optimized immobilization for GOx, enables better performance as a glucose biosensor, and allows the prediction of some outcomes., Competing Interests: Declarations. Conflict of interest: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J. Ledesma-García reports financial support was provided by Mexican Council for Humanities, Sciences and Technologies. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

A novel self-powered and flexible enzymatic biofuel cell (EBFC)-based aptasensor was developed for the sensitive and selective detection of 17 β-estradiol (E2). A flexible polyvinyl alcohol (PVA)-tannic acid‑carbon nanotube/reduced graphene oxide (PTCR) substrate was modified with gold nanoparticles (AuNPs) and thiolated aptamer 1 (Apt1) to yield Apt1@AuNPs/PTCR. A copper-based metal-organic framework (Cu-MOF) with peroxidase mimicking activity was employed to anchor glucose oxidase (GOD) and Apt2, forming the Cu-MOF@GOD/Apt2 tag. When E2 was recognized by Apt1, the anchored E2 quantitatively recognized Cu-MOF@GOD/Apt2 to create a Cu-MOF@GOD/Apt2-E2-Apt1 sandwich structure for glucose oxidation to generate electrical power. Increased E2 concentrations enhanced Cu-MOF@GOD/Apt2 capture and amplified the electrical signal. The electrical power increased linearly as the E2 concentration increased from 1.0 pM to 1.0 nM. The sensor was successfully applied to various food samples and blood serum detection. This work promoted the application of novel self-powered biosensors for food safety analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Herein, a comparative study between novel water-soluble phthalocyanine-based biosensors was performed for the application of glucose sensing. For this purpose, two different copper (II) and manganese (III) phthalocyanines and their water-soluble derivatives were synthesized, and then their role as a supporting material for enzyme immobilization was evaluated by comparing their sensor performances. Two different phthalocyanine (AP-OH 2 -MnQ (MnPc) and AP-OH 2 -CuQ (CuPc)) were tested using electrochemical biosensor with immobilized glucose oxidase (GOx). To the best of our knowledge, the related water-soluble phthalocyanine-based glucose biosensors were attempted for the first time, and the developed approach resulted in improved biosensor characteristics. The constructed biosensors GE/MnPc/GOx and GE/CuPc/GOx showed good linearity between 0.003-1.0 mM and 0.05-0.4 mM, respectively. The limit of detection was estimated at 0.0026 mM for the GE/MnPc/GOx and 0.019 mM for the GE/CuPc/GOx. K M app and sensitivity values were also calculated as 0.026 mM and 175.043 µAmM -1 cm -2 for the GE/MnPc/GOx biosensor and 0.178 mM and 117.478 µAmM -1 cm -2 for the GE/CuPc/GOx biosensor. Moreover, the fabricated biosensors were successfully tested to detect glucose levels in beverages with high recovery results. The present study shows that the proposed water-soluble phthalocyanines could be a good alternative for quick and cheap glucose sensing with improved analytical characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hyperglycemia provides a favorable breeding ground for bacteria, resulting in repeated and persistent inflammation of wounds and prolonged healing processes. In this study, platinum (Pt) nanoparticles (NPs) and glucose oxidase (GOx) were decorated on the surface of camelina lipid droplets (OB) linked with hFGF2, forming PGOB through in situ reduction of Pt ions and electrostatic adsorption, respectively. PGOB exhibits cascade enzyme catalytic activity, which can be activated by glucose in diabetic wound tissues. Specifically, GOx on PGOB catalyzes glucose into hydrogen peroxide, which can further decompose into hydroxyl radicals that have higher toxicity for bacterial inactivation. Additionally, glucose decomposition creates a low pH microenvironment, facilitating the cascade catalytic activity that ensures better bacterial suppression within the wound tissues. Furthermore, hFGF2 promotes the proliferation and migration of fibroblasts. Both in vitro and in vivo experiments confirm that PGOB effectively accelerates wound healing processes through bacteria inactivation and tissue regeneration. This study has developed an alternative strategy for glucose-triggered synergistic cascade therapy for diabetic wounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Enzymatic cascade reactions with high activity and specificity in living cells always benefit from multicompartmentalized organelles that provide separately confined spaces for enzymes, avoiding their mutual interference to ensure the high-efficiency operation of necessary vital movements. Inspired by this, we designed a 3D spherical microreactor (Au@H-APF@Pt) with biomimetic cascade catalysis for glucose detection. First, ultrasmall gold nanoparticles were immobilized in situ on the internal cavities of hollow 3-aminophenol formaldehyde resin (H-APF) nanospheres, along with glucose oxidase activity. Then, platinum nanoparticles (PtNPs) with peroxide-like activity were reduced surrounding the outer layer of the H-APF nanospheres. Similar to the cell structure, different metal sites in this bifunctional microreactor operated independently, bringing higher catalytic activity and selectivity and thus being synergistically capable of a cascade reaction to catalyze the substrate for glucose detection. This cell-mimicking microreactor (Au@H-APF@Pt) was successfully applied in glucose colorimetric detection, showing a 1.9-fold activity enhancement compared to direct mixing (Au/Pt). The observed low catalytic activity was attributed to the extended time for transferring hydrogen peroxide (H 2 O 2 ) from Au NPs to the solution and then to PtNPs. Integrating a smartphone APP, a real-time, visual, and Au@H-APF@Pt-based hydrogel sensor for glucose detection was also proposed. Satisfactory results highlight that this cell-mimicking microreactor offers a very successful strategy to improve the efficiency of cascade catalysis systems in biosensing.

Diabetes management demands precise monitoring of key biomarkers, particularly insulin (I) and glucose (G). Herein, we present a bioelectronic chip device that enables the simultaneous detection of I and G in biofluids within 2 min. This dual biosensor chip integrates aptamer-based insulin sensing with enzymatic glucose detection on a single platform, employing a four-electrode sensor chip. The insulin voltammetric sensor employs a G-quadraplex methylene-blue-modified aptamer, while the amperometric biocatalytic glucose sensor utilizes a second-generation mediator-based approach. Simultaneous reagent-less sensing of I and G has been achieved by addressing key challenges. These include combining different surface chemistries, assay formats, and detection principles at closely spaced working electrodes and the substantially different concentration levels of the I and G targets. An attractive analytical performance, with no apparent crosstalk, is demonstrated for the simultaneous detection of millimolar G concentrations and picomolar I concentrations in single microliter serum or saliva sample droplets. This dual biosensor offers rapid, cost-effective, and reliable monitoring, addressing the unmet need for integrated multiplexed diabetes biomarker detection in decentralized settings. Such integration of enzymatic and aptamer-based bioassays could greatly expand the scope of decentralized testing in healthcare beyond diabetes care.

Wearable patch biosensors for noninvasive and continuous diabetes management through sweat glucose analysis present a promising prospect. However, how to obtain sweat samples safely and effectively remains a huge challenge, especially in a resting state. In this work, we propose an innovative wearable patch biosensor through a heat-stimulated approach for sweat collection. A silver nanowire-loaded electrothermal film was designed as the heat source to stimulate sweat glands for sweat secretion. Subsequently, the secreted sweat sample was transported and enriched through microfluidic channels, which was continuously and sensitively analyzed by a Prussian blue and glucose oxidase comodified glucose electrochemical biosensor. Under optimal conditions, its sensitivity could achieve 14 μM sweat glucose within 15 min, which was 17 min shorter than that without heating. The specificity, reproducibility, and accuracy were also adequate. To achieve on-body perspiration monitoring of human subjects, the wearable patch biosensor was integrated with a portable electrochemical workstation, a temperature controller, and a power source. The glucose concentration was presented on a smartphone. Results showed that the glucose concentration in sweat detected by the wearable biosensor presented a highly consistent trend with the blood glucose measured by a blood glucose meter throughout the day with normal meals. Compared with other conventional sweat stimulation strategies, the simple device and safe principle made it more suitable for individuals who were sedentary or at rest. This work provides a new approach to realizing wearable patch biosensors for personalized health monitoring.

Detecting glucose levels is crucial for diabetes patients as it enables timely and effective management, preventing complications and promoting overall health. In this endeavor, we have designed a novel, affordable point-of-care diagnostic device utilizing microfluidic principles, a smartphone camera, and established laboratory colorimetric methods for accurate glucose estimation. Our proposed microfluidic device comprises layers of adhesive poly-vinyl films stacked on a poly methyl methacrylate (PMMA) base sheet, with micro-channel contours precision-cut using a cutting printer. Employing the gold standard glucose-oxidase/peroxidase reaction on this microfluidic platform, we achieve enzymatic glucose determination. The resulting colored complex, formed by phenol and 4-aminoantipyrine in the presence of hydrogen peroxide generated during glucose oxidation, is captured at various glucose concentrations using a smartphone camera. Raw images are processed and utilized as input data for a 2-D convolutional neural network (CNN) deep learning classifier, demonstrating an impressive 95% overall accuracy against new images. The glucose predictions done by CNN are compared with ISO 15197:2013/2015 gold standard norms. Furthermore, the classifier exhibits outstanding precision, recall, and F1 score of 94%, 93%, and 93%, respectively, as validated through our study, showcasing its exceptional predictive capability. Next, a user-friendly smartphone application named "GLUCOLENS AI" was developed to capture images, perform image processing, and communicate with cloud server containing the CNN classifier. The developed CNN model can be successfully used as a pre-trained model for future glucose concentration predictions., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Insufficient accumulation of reactive oxygen species (ROS) due to tumor hypoxia significantly contributes to increased radiation resistance and the failure of radiotherapy (RT). Therefore, developing methods to alleviate hypoxia and boost ROS levels represents a promising strategy for enhanced radiosensitivity. This study introduced a self-cascade catalytic Pt@Au nanozymes as a radiosensitizer, using glucose oxidase (GOx)-, catalase (CAT)-, and peroxidase (POD)-like activities to improve hypoxia and increase ROS accumulation, thereby affecting glucose metabolism and enhancing the effects of RT. Pt@Au nanozymes exhibit GOx-like activity, which not only depletes glucose to induce starvation therapy, but also generates hydrogen peroxide (H 2 O 2 ) for cascade reactions. Moreover, Pt@Au nanozymes demonstrate CAT-like activity, catalyzing the conversion of H 2 O 2 to O 2 . This conversion effectively alleviates hypoxia, stabilizes ROS, increases DNA damage, significantly enhancing RT efficacy and sustaining the effects of starvation therapy. As high-Z materials, Pt@Au nanozymes can deposit more X-ray energy. Furthermore, the POD-like activity catalyzes the conversion of H 2 O 2 into highly reactive hydroxyl radicals (·OH), which increases ROS levels and enhances RT. Pt@Au nanozymes serve as X-ray computed tomography (CT) imaging agents, allowing for clear differentiation between tumor and normal tissue boundaries and enhancing the precision of RT. In summary, Pt@Au nanozymes serve as effective radiosensitizers by depleting glucose to induce starvation therapy, enhancing cascade reactions, and inhibiting tumor proliferation. Through their self-cascade reactions, these nanozymes dramatically increase oxygen levels within tumors, reduce hypoxia, and enhance ROS levels. This advancement addresses the radioresistance associated with hypoxic tumors, paving the way for innovative strategies in RT.

Cascading enzymatic therapy is a promising approach in cancer treatment. However, its effectiveness is often hindered by enzyme inactivation, limited exposure of active sites, cancer cell self-protection mechanisms such as autophagy, and non-specific toxicity, which can lead to treatment failure. To address these challenges, we used a low-temperature aqueous-phase synthesis method to create semi-crystalline, water-dispersible fluorescent COF nanospheres. These nanospheres can stably load glucose oxidase (GOx) and ultrafine Fe 2 O 3 nanozymes, allowing for convenient coating with tumor cell membranes to form a uniform tumor-targeted cascading enzymatic nanosystem (CFGM). This system promotes a cycle of tumor glucose depletion, reactive oxygen species (ROS) generation, and oxygen production, facilitating tumor-targeted starvation therapy (ST) and chemodynamic therapy (CDT). Notably, the semi-crystalline COF carrier within this system can degrade slowly under mildly acidic conditions, forming large aggregates that damage lysosomes and disrupt lysosomal autophagy, thereby eliminating the autophagy protection of cancer cells activated by the combined ST. This synergistic approach enhances the catalytic inhibition of tumors. Our research thus provides an alternative COF-based platform and strategy for effective cancer treatment.

Disposable biosensors provide high portability and advantageous response time, which are crucial in the next generation of analytical platforms. Herein, we report on zeolites embedding silver clusters as an electroactive material that enhances the electrode-analyte interaction in disposable electrochemical strips made of plastic or paper. The resulting analytical platform effectively immobilizes analytes and facilitates electron exchange transfer. Two detection mechanisms were explored in the electrodes decorated with zeolites embedding silver clusters. The oxidative-reductive character of zeolites embedding silver clusters was applied for chloride ion detection, which is suitable for environmental analysis. Additionally, the electrocatalytic activity of the composite was applied in glucose sensing in the presence of glucose oxidase, demonstrating the versatility of the composites for detecting molecules of a different nature (clinically or environmentally relevant) without further modification. Our approach contributes to the development of simple and low-cost modification procedures for integrating electroactive materials into miniaturized electrochemical sensors for portable platforms and point-of-care devices.

Rapid enzyme immobilization is essential for enzyme catalysis and sensing applications, yet constructing effective immobilization systems is challenging due to the need to balance enzyme activity with the properties of the surrounding framework. Herein, taking glucose oxidase (GOx) as a model, a rapid and straightforward approach was presented for synthesizing palladium nanoparticles (PdNPs)-decorated GOx encapsulated in HOF-101 nanocomposite materials (designated as PdNPs/GOx@HOF-101) through an in situ photoreduction and enzyme-triggering HOF-101 encapsulation. The enzyme's surface residues trigger the nucleation of HOF-101 around it through the hydrogen-bonded bio interface, completing the self-assembly of HOF-101 in 0.5 h. Furthermore, the biocomposites loaded with ultrafine PdNPs show satisfactory photoelectrochemical (PEC) properties. As a proof-of-concept, a PEC biosensor was constructed by utilizing PdNPs/GOx@HOF-101 as a photoactive probe, which can quickly and sensitively detect glucose and simultaneously remain stable within the circumstance of 30-60 °C and pH 4-8. These attributes pave the way for diverse applications, including improved enzyme immobilization techniques, advanced biosensors, and more efficient biocatalytic processes.

Peptides and their conjugates are appealing as molecular scaffolds for constructing supramolecular biomaterials from the bottom up. Through strategic sequence design and interaction modulation, these peptides can self-assemble into diverse nanostructures that can, in turn, mimic the structural and catalytic functions of contemporary proteins. Here, inspired by the histidine brace active site identified in the metalloenzyme, we developed a triblock polypeptide with a hydrophobic polyleucine segment, a hydrophilic polylysine segment, and a terminal oligohistidine segment. This polypeptide demonstrates tunable and adaptive self-assembly morphologies. Moreover, copper ions can interact with the oligohistidine chelator and mediate the supramolecular assembly, generating metal-ligand centers for redox flow. The triblock polypeptide-based peptide micelles show Fenton-type activity with high substrate affinity when coassembled with copper ions. We have also engineered therapeutic micelles by coassembling two polypeptides, one integrated with copper ions and the other conjugated with glucose oxidase. This coassembled nanoplatform shows high in vitro and in vivo antitumor efficacy through a mechanism that combines triggered starvation and chemodynamic therapy. The versatility of this polypeptide sequence, which is compatible with various metal ions and functional ligands, paves the way for a broad spectrum of therapeutic and diagnostic applications.

Chemodynamic therapy (CDT) has been limited by the tumor microenvironment, such as the low concentration of hydrogen peroxide (H 2 O 2 ). The combination of therapeutic strategies that increase H 2 O 2 with CDT can synergistically enhance the therapeutic effect. Herein, a novel supramolecular PEG-DNA-ferrocene nanogel that can codeliver glucose oxidase (GOx) and the hypoxia-activable prodrug tirapazamine (TPZ) was developed to synergistically amplify CDT via cascade reactions. The DNA nanogel was size-controllable and DNase I-responsive and exhibited good biocompatibility. Induced by oxygen consumption and H 2 O 2 generation in the catalytic reaction of GOx, the drugs TPZ and ferrocene in the nanogel underwent the hypoxia-based reaction and the Fenton reaction, respectively. The vitro model tests, intracellular ROS test, MTT experiments, and DNA damage assay demonstrated that the H 2 O 2 -based cascade Fenton reaction and the hypoxia-based cascade reaction obviously increased ·OH generation and promoted the apoptosis of cancer cells. This cascade supramolecular nanoplatform provided a promising therapeutic strategy to synergistically amplify CDT.

Point-of-care (POC) tests increasingly highlight the importance of portable, cost-effective, and visually quantitative detection of biomarkers. Herein, we developed a power-free and visual signal-readout POC sensor based on the target-triggered ultrafast gelation process. In the gelation process, the target triggered the cascade reaction catalyzed by oxidase and ferrous glycinate to produce carbon radicals that immediately initiated the rapid polymerization and cross-linking of acryloylated chondroitin sulfate and dimethylacrylamide. This highly efficient enzymatic polymerization process contributed to the ultrafast generation of chondroitin hydrogel within 1 min at 25 °C. The increase in viscosity of aqueous solution resulted from hydrogel formation was then visually measured according to the distance of solution migration on a tick-labeled pH test strip, which thus realized the quantification of a target. By utilizing glucose oxidase as an oxidase model during the gelation process, this POC sensor was successfully employed in the rapid quantitative detection of glucose without the need for any auxiliary instruments. Benefiting from the specificity and stability of the enzymatic polymerization reaction, the sensor exhibited excellent performance in the detection of glucose in clinical blood samples. Moreover, the sensor was further extended to uric acid detection and enabled accurate assay in clinical urine samples, which indicated the versatility and practicability of this sensor in the POC test.

Existing strategies to investigate the antitumor effects of artemisinin and its derivatives (ART) are inadequate. Both free Fe(II) and heme in mitochondria have been proposed to be ART activators. However, the two impact factors have been considered separately or have not been thoroughly investigated. Here, the designed ART-based novel nanosystem with transferrin-modified hollow mesoporous silica nanoparticles as drug-delivery carriers is loaded with a functional artemisinin derivative (Cou-DHA), glucose oxidase, and perfluoropentane inside the cavity, which can enhance synergistic Fe(II)-ART-mediated chemodynamic therapy (CDT). Under the action of H 2 O 2 generated by starvation therapy, the Fenton reaction occurs with Fe(III) in transferrin converted into free Fe(II). Remarkably, this report is the first to provide Fe(II) to ART actively and efficiently by combining starvation therapy and Fenton reaction-based CDT. Importantly, mitochondria-targeted Cou-DHA delivers ART into the mitochondria to sensitize the anticancer effects of ART with the supplied Fe(II) to realize Fe(II)-ART-mediated CDT. The ART-based novel nanosystem developed in our work thus has great potential for exploitation in advanced cancer therapies.

Biofilm formation is a major challenge in the treatment of tuberculosis, leading to poor treatment outcomes and latent infections. The complex and dense extracellular polymeric substances (EPS) of the biofilm provides safe harbour for bacterium enabling persistence against anti-TB antibiotics. In this study, we demonstrated that rifampicin-encapsulated silk fibroin nanoparticles immobilized with antibiofilm enzymes can disrupt the Mycobacterium smegmatis biofilm and facilitate the anti-bacterial action of Rifampicin (RIF). The EPS of M.smegmatis biofilm predominantly comprised of lipids (48.8 ± 1.32 %) and carbohydrates (34.8 ± 4.70 %), similar to tuberculosis biofilms. Pre-formed biofilm eradication screening revealed that hydrolytic enzymes such as β-Glucosidase, Glucose oxidase, ɑ-Amylase, Acylase, and Phytase can exhibit biofilm eradication of M.smegmatis biofilms. The enzyme-mediated biofilm disruption was associated with a decrease in hydrophobicity of biofilm surfaces. Treatment with β-glucosidase and Phytase demonstrated a putative biofilm eradication by reducing the total carbohydrates and lipid composition without causing any significant bactericidal activity. Further, Phytase (250 μg/ml) and β-Glucosidase (112.5 ± 17.6 μg/ml) conjugated rifampicin-loaded silk fibroin nanoparticles (R-SFNs) exhibited an enhanced anti-bacterial activity against pre-formed M.smegmatis biofilms, compared to free rifampicin (32.5±7 μg/ml). Notably, treatment with β-glucosidase, Phytase and ɑ-amylase immobilized SFNs decreased the biofilm thickness by ∼98.84 % at 6h, compared to control. Thus, the study highlights that coupling anti-mycobacterial drugs with biofilm-eradicating enzymes such as amylase, phytase or β-glucosidase can be a potential strategy to improve the TB therapeutic outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships with individual or other organization that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Utilizing enzyme cascades as a promising approach for targeted cancer therapies holds significant potential, yet its clinical effectiveness is substantially hindered by functional losses during delivery. Complex coacervation emerges as an intriguing strategy for designing functional nanoreactors. In this study, a noteworthy achievement is presented in the development of lactobionic acid-modified tumor microenvironment (TME)-responsive polyelectrolyte complex vesicles (HGS-PCVs) based on bioinspired homopolypeptoids, which serve as a facile, intelligent, and highly efficient nanoreactor tunable for glucose oxidase, hemoglobin, and sorafenib (SRF) to hepatic cancer cells. The TME-responsive permeability of HGS-PCVs enables the selective entry of glucose into their interior, triggering an enzymatic cascade reaction within the tumor. This intricate process generates toxic hydroxyl radicals while concurrently lowering the pH. Consequently, this pH shift enhances the SRF release, effectively promoting ferroptosis and apoptosis in the target cancer cells. Further, the administration of the HGS-PCVs not only initiates immunogenic cell death but also plays a crucial role in inducing the maturation of dendritic cells within lymph nodes. It stimulates an adaptive T-cell response, a crucial mechanism that contributes to impeding the growth of distant tumors in vivo, demonstrating the promising potential of PCVs for cancer immunotherapy., (© 2024 Wiley‐VCH GmbH.)

A surface plasmon resonance imaging (SPRI)-based biosensor is demonstrated for the detection of both hydrogen peroxide (H 2 O 2 ) and glucose. The H 2 O 2 to be detected acts as an oxidant and etch the silver film. This process gradually effects on resonance condition and consequently the reflected light intensity at a fixed angle. The etching rate of the silver film shows a clear relation with the H 2 O 2 concentration. Therefore, monitoring the reflected light intensity progressively changing over a few minutes, enables accurate detection of H 2 O 2 concentrations ranging from 0 to 200 μM (within physiological range of 0.25-50 μM), with a remarkable limit of detection (LOD) as low as 40 nM. In this regard, the behavior of the surface plasmon resonance (SPR) dip in response to the reduction of the silver film thickness is predicted by Winspall simulation software. These simulation results are in good agreement with the experimental results. Moreover, the proposed method can be applied to determine glucose concentrations ranging from 0 to 10 mM, encompassing the physiological range of 3-8 mM. This is achieved by observing the generated H 2 O 2 through the enzymatic oxidation reaction between glucose and glucose oxidase (Gox). The sensor demonstrates remarkable sensitivity and selectivity, with a detection limit as low as 175 μM for glucose concentration. Furthermore, accurate measurement of glucose concentration in an actual human serum sample is achievable with the proposed sensor, using the standard addition method. The suggested glucose sensor shows promising prospects for use in routine glucose testing, employing a label-free, real-time, and multiplex detection approach.© 2017 Elsevier Inc. All rights reserved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Enzyme catalytic cascade reactions based on peroxidase nanozymes and natural enzymes have aroused extensive attention in analytical fields. However, a majority of peroxidase nanozymes perform well only in acidic environments, resulting in their optimal pH mismatch with a neutral pH of natural enzymes, further restricting their application in biochemical sensing. Herein, Mn-doped CeO 2 (Mn/CeO 2 ) performing enhanced peroxidase-like activity at neutral conditions was prepared via a facile and feasible strategy. An effective enzyme cascade catalysis system via integrating glucose oxidase (GOx) with Mn/CeO 2 was developed for one-pot detection of glucose in serum at neutral conditions. Using one-pot multistep catalytic reactions, this work provided a detection platform that allows for faster detection and easier operations than traditional methods. Under optimized conditions, our assay performed a sensitive detection of glucose ranging from 2.0 μΜ to 300 μΜ and a low detection limit of 0.279 μΜ. Notably, favorable analytical outcomes for glucose detection in serum samples were obtained, exhibiting potential applications in clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quarantine plant bacteria (QPB) are significant component of invasive alien species that result in substantial economic losses and serious environmental damage. Herein, a colorimetric aptasensor has been proposed based on the sandwich structure and the cascaded catalytic strategy for on-site detecting Xanthomonas hyacinthi, a type of QPB, in natural environments. The self-screened aptamer obtained through SELEX can bind to specific sites on the surface of viable organism with high affinity and specificity, which guarantees the selectivity of aptasensor. As an important part of the aptasensor, MIL-88-NH 2 (Fe) not only acts as a multifunctional carrier for both aptamers and glucose oxidase, but also catalyzes enzyme-like reaction because of specific surface area, amino and peroxidase-like activity. The present of Xanthomonas hyacinthi can trigger the formation of a sandwich structure and the occurrence of cascade catalytic reaction, enabling the detection with UV-Vis spectra and naked eyes. The proposed aptasensor presents a low detection limit of 2 cfu/mL and a wide linear range of 10 -10 7  cfu/mL. Compared to traditional detection methods for QPB, the reasonable design, high selectivity and convenience significantly improve the detection efficiency and contribute to environmental protection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Metal-organic frameworks (MOFs), especially bimetallic MOFs, have attracted widespread attention for simulating the structure and function of natural enzymes. In this study, different morphologies of bimetallic Cu-Zn-MOF with different peroxidase (POD)-like activities were prepared by simply controlling the molar ratio of Cu 2+ and Zn 2+ . Among them, the doughnut-shaped Cu 9 -Zn 1 -MOF exhibited the largest POD-like activity. Cu 9 -Zn 1 -MOF was combined with glucose oxidase to construct a sensitive and selective glucose colorimetric biosensor with a linear detection range of 10-300 μM and a detection limit of 7.1 μm. Furthermore, Cu 9 -Zn 1 -MOF can efficiently convert hydrogen peroxide (H 2 O 2 ) into hydroxyl radicals that effectively kill both gram-negative and gram-positive bacteria at low H 2 O 2 level. The results of this study may promote the synthesis of bimetallic MOFs and broaden their applications in the biomedical field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Regular blood glucose monitoring and control is necessary for people with type 1 or advanced type 2 diabetes, yet diagnosing and treating patients with diabetes in an accurate, sustained and patient-friendly manner remains limited. Here, a glucose-responsive bifunctional nanosystem (PGOxMns) is constructed via one-pot biomineralisation of manganese dioxide with glucose oxidase and ε-poly-L-lysine. Under hyperglycaemic conditions, the cascade reactions that occur when glucose interacts with PGOxMns can trigger the production of Mn(II), which enhances the magnetic resonance imaging signal. Simultaneously, manganese dioxide catalyses the decomposition of toxic hydrogen peroxide into oxygen, which also maintains glucose oxidase (GOx) activity. In an in vivo model of diabetes, PGOxMns is used to monitor glucose levels (0-20 mm) and allowed identification of diabetic mice via T 1 -weighted MRI. Furthermore, PGOxMns is found to have a high insulin-loading capacity (83.6%), likely due to its positive charge. A single subcutaneous injection of insulin-loaded nanosystem (Ins-PGOxMns) into diabetic mice resulted in a rapid and efficient response to a glucose challenge and prolonged blood glucose level control (< 200 mg dL -1 ) for up to 50 h. Overall, this proof-of-concept study demonstrates the feasibility of using biomineralised nanosystems to develop patient-friendly strategies for glucose monitoring and control., (© 2024 Wiley‐VCH GmbH.)

The amplification strategies used for self-powered biosensor based on biofuel cell (BFC-SPB) need to be further developed. Because the currently developed strategies utilized the complicated hybridization of DNA or poorly readable current signal of capacitors for amplification, which limits the practical application in public health emergencies. Here, we present a facile chemical amplification strategy for BFC-SPB. The 5-min amplification was triggered by simply adding H 2 O 2 solution dropwise to the sensing cathode after the formation of the immune sandwich. The Ag NP of immunoprobe were oxidized to Ag(I), which can be served as the electron acceptor of the cathode. The amount of immunoprobe was positively correlated with that of the antigen, resulting in corresponding and high concentration of Ag(I) after the amplification, which enhanced the ability of the cathode as the electron acceptor. Meanwhile the glucose oxidation reaction (GOR) was performed on the bioanode modified with glucose oxidase (GOx). After assembling the bioanode and sensing cathode, the open circuit voltage of the BFC-SPB, measured by digital multimeter, distinctly rised with the elevated concentration of the antigen. To demonstrate the proof of concept, immunoglobulin G (IgG), selecting as a model analyte, was sensitively detected using this method. Result indicated that the limit of detection was 4.4 fg mL -1 (0.03 amol mL -1 ) in the linear range of 1 pg mL -1 -10 μg mL -1 . This work initiates a brand-new way of chemical amplification strategy for BFC-SPB, and offers a promising platform for practical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Natural and artificial enzyme oxygen-generating systems for photodynamic therapy (PDT) are developed for tumor treatment, yet they have fallen short of the desired efficacy. Moreover, both the enzymes and photosensitizers usually need carriers for efficient delivery to tumor sites. Here, a self-cascade-enhanced multimodal tumor therapy is developed by ingeniously integrating self-cascade-enhanced PDT with Zn 2+ -overloading therapy. Manganese-porphyrin (TCPP-Mn) is chosen both as the photosensitizer and catalase (CAT) mimic, which can be encapsulated within glucose oxidase (GOx). Acid-responsive zeolitic imidazolate framework-8 (ZIF-8) is applied as the carrier for TCPP-Mn@GOx (T@G), attaining TCPP-Mn@GOx@ZIF-8 (T@G@Z). T@G@Z demonstrates robust anti-tumor ability as follows: upon the structural degradation of ZIF-8, GOx can mediate the oxidation of glucose and generate hydrogen peroxide (H 2 O 2 ); TCPP-Mn can catalyze H 2 O 2 into O 2 for self-cascade-enhanced PDT; meanwhile, the released Zn 2+ can enhance oxidative stress and induce mitochondrial dysfunction by destroying mitochondrial membrane potential; furthermore, immunotherapy can be activated to resist primary tumor and tumor metastasis. The self-cascade-enhanced T@G@Z exhibited its potential application for further tumor management., (© 2024 Wiley‐VCH GmbH.)

Recently, gold nanomaterials have been rapidly developed owing to their high stability, good biocompatibility, and multifunctionality. The unique catalytic activity of gold nanomaterials has driven the emergence of the concept for a "gold nanozyme." Understanding the characteristics of gold nanozymes is crucial for improving their catalytic performance as well as expanding their applications. In this review, we provide an overview of the intrinsic enzyme-like activities of gold nanozymes, including peroxidase-, catalase-, superoxide dismutase-, and glucose oxidase-like activities, and the catalytic mechanisms involved. In addition, strategies for modulating the catalytic activity of gold nanozymes and their applications in biosensing were discussed in detail. Moreover, we highlight the current challenges of gold nanozymes and look forward to attracting more attention for propelling the developments in this field., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The transformation of monotherapy into multimodal combined targeted therapy to fully exploit synergistic efficacy is of increasing interest in tumor treatment. In this work, a novel nanodrug-carrying platform based on iron-based MOFs, which is loaded with doxorubicin hydrochloride (DOX), dihydroartemisinin (DHA), and glucose oxidase (GOx), and concurrently covalently linked to the photosensitizer 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) in polydopamine (PDA)-encapsulated MIL-101(Fe) (denoted as MIL-101(Fe)-DOX-DHA@TCPP/GOx@PDA, MDDTG@P), is successfully developed. Upon entering the tumor microenvironment, MDDTG@P catalyzes the hydrogen peroxide (H 2 O 2 ) into hydroxyl radicals (·OH) and depletes glutathione (GSH); thus, exerting the role of chemodynamic therapy (CDT). The reduced Fe 2+ can also activate DHA, further expanding CDT and promoting tumor cell apoptosis. The introduced GOx will rapidly consume glucose and oxygen (O 2 ) in the tumor; while, replenishing H 2 O 2 for Fenton reaction, starving the cancer cells; and thus, realizing starvation and chemodynamic therapy. In addition, the covalent linkage of TCPP endows MDDTG@P with good photodynamic therapeutic (PDT) properties. Therefore, this study develops a nanocarrier platform for triple synergistic chemodynamic/photodynamic/starvation therapy, which has promising applications in the efficient treatment of tumors., (© 2024 Wiley‐VCH GmbH.)

A simple and sensitive method for Cu 2+ detection was developed using the Cu + -catalyzed alkyne-azide cycloaddition reaction, Fe 3 O 4 magnetic nanoparticles (MNPs) as the reaction platform, and a portable blood glucose meter (PGM) as the detection method. Gold nanoparticles (AuNPs) were labeled with glucose oxidase (GOx) and alkyne-functionalized, terminally thiolated ssDNA (C2). In the presence of Cu 2+ and ascorbate, the functionalized AuNPs were captured onto MNPs modified with azide-functionalized ssDNA (C1) via the Cu + -catalyzed alkyne-azide cycloaddition reaction. The GOx on the AuNPs' surface oxidized glucose (Glu) into gluconic acid and H 2 O 2 , reducing the Glu content in the reaction solution, which was quantitatively detected by the PGM. Under optimal conditions, the PGM response of the system showed a good linear relationship with the logarithm of Cu 2+ concentration in the range of 0.05 to 10.00 μmol/L, with a detection limit of 0.03 μmol/L (3σ). In actual tap water samples, the spiked recovery rate of Cu 2+ was between 92.30% and 113.33%, and the relative standard deviation was between 0.14% and 0.34%, meeting the detection requirements for Cu 2+ in real water samples.

Organic photoelectrochemical transistor (OPECT) has emerged as a promising technique for biomolecule detection, yet its operational rationale remains limited due to its short development time. This study introduces a stable tandem catalysis protocol by synergizing the enzyme-incorporated metal-organic frameworks (E-MOFs) with polyoxometalate (POM) nanozyme for sensitive OPECT bioanalysis. The zeolitic imidazolate framework-8 (ZIF-8) acts as the skeleton to protect the encapsulated glucose oxidase (GOx), allowing the stable catalytic generation of H 2 O 2 . With peroxidase-like activity, a phosphotungstic acid hydrate (PW 12 ) is then able to utilize the H 2 O 2 to induce the biomimetic precipitation on the photogate, ultimately resulting in the altered device characteristics for quantitative detection. This work reveals the potential and versatility of an engineered enzymatic system as a key enabler to achieve novel OPECT bioanalysis, which is believed to offer a feasible framework to explore new operational rationale in optoelectronic and bioelectronic detection.

Sonodynamic therapy (SDT) has been extensively studied as a new type of non-invasive treatment for mammary cancer. However, the poor water solubility and defective biocompatibility of sonosensitizers during SDT hinder the sonodynamic efficacy. Herein, a nanoplatform has been developed to achieve high efficient SDT against mammary cancer through the host-guest interaction of β-cyclodextrin/5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (β-CD-TPP) and ferrocenecarboxylic acid/chitooligosaccharides (FC-COS). Moreover, the glucose oxidase (GOx) was loaded through electrostatic adsorption, which efficiently restricts the energy supply in tumor tissues, thus enhancing the therapeutic efficacy of SDT for tumors. Under optimal conditions, the entire system exhibited favorable water solubility, suitable particle size and viable biocompatibility. This facilitated the integration of the characteristics of starvation therapy and sonodynamic therapy, resulting in efficient inhibition of tumor growth with minimal side effects in vivo. This work may provide new insights into the application of natural oligosaccharides for construct multifunctional nanocarrier systems, which could optimize the design and development of sonodynamic therapy strategies and even combination therapy strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Multidrug-resistant (MDR) bacteria-infected wound healing remains greatly challenging, especially in diabetic patients. Herein, a novel nano-drug delivery based on endogenous glucose-driven cascade reaction is proposed for boosting MDR bacteria-infected diabetic wound healing with high efficacy by improving wound microenvironment and enhancing photodynamic antibacterial activity. The composite nanoagent is first self-assembled by integrating berberine (BBR) and epigallocatechin gallate (EGCG) from natural plant extracts, named as BE NPs , which is successively coated with manganese dioxide nanoshells (MnO 2 NSs ) and glucose oxidase (GOX) to form the final BEMG NPs . The cascade reaction is triggered by glucose at the wound site of diabetes which is specifically catalyzed by GOX in the BEMG NPs to produce gluconic acid and hydrogen peroxide (H 2 O 2 ). That is subsequently to decompose MnO 2 NSs in the BEMG NPs to generate oxygen (O 2 ). The BEMG NPs as photosensitizers effectively produce reactive oxygen species (ROS) to enhance the eradication of bacteria with the assistance of O 2 . Under the synergistic function of the cascaded reaction, the BEMG NPs present excellent antibacterial efficacy even for MDR bacteria. The in vivo experiments explicitly validate that the constructed nano-drug delivery can augment the MDR bacteria-infected diabetic wound healing with excellent biosafety. The as-proposed strategy provides an instructive way to combat ever-threatening MDR bacteria, which particularly is beneficial for diabetic patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aims to design microgels for controlled drug release via enzymatically generated pH changes in the presence of glucose. Modern medicine is focused on developing smart delivery systems with controlled release capabilities. In response to this demand, we present the synthesis, characterization, and enzymatically triggered drug release behavior of microgels based on poly(acrylic acid) modified with glucose oxidase (GOx) (p(AA-BIS)-GOx). TEM images revealed that the sizes of air-dried p(AA-BIS)-GOx microgels were approximately 130 nm. DLS measurements showed glucose-triggered microgel size changes upon glucose addition, which depended on buffer concentration. Enzymatically triggered drug release experiments using doxorubicin-loaded microgels with immobilized GOx demonstrated that drug release is strongly dependent on glucose and buffer concentration. The highest differences in release triggered by 5 and 25 mM glucose were observed in HEPES buffer at concentrations of 3 and 9 mM. Under these conditions, 80 and 52% of DOX were released with 25 mM glucose, while 47 and 28% of DOX were released with 5 mM glucose. The interstitial glucose concentration in a tumor ranges from ∼15 to 50 mM. Normal fasting blood glucose levels are about 5.5 mM, and postprandial (2 h after a meal) glucose levels should be less than 7.8 mM. The obtained results highlight the microgel's potential for drug delivery using the enhanced permeability and retention (EPR) effect, where drug release is controlled by enzymatically generated pH changes in response to elevated glucose concentrations.

Quercetin (QR) is a natural flavonoid with strong anti-inflammatory properties, but it suffers from poor water solubility and bioavailability. Micro/nanomotors (NMs) are tiny devices that convert external energy or chemical fuels into an autonomous motion. They are characterized by their small size, rapid movement, and self-assembly capabilities, which can enhance the delivery of bioactive ingredients. The study synthesized natural polysaccharide-based nanotubes (NTs) using a layer-by-layer self-assembly method and combined with urease (Ure), glucose oxidase (GOx), and Fe 3 O 4 to create three types of NMs. These NMs were well-dispersed and biocompatible. In vitro experiments showed that NMs-Fe 3 O 4 has excellent photothermal conversion properties and potential for use in photothermal therapy. Cellular inflammation model results demonstrated that QR-loaded NMs were not only structurally stable but also improved bioavailability and effectively inhibited the release of inflammatory mediators such as IL-1β and IL-6, providing a safe and advanced carrier system for the effective use of bioactive components in food.

Macrophages are usually present in solid tumors where they participate in tumor progression, angiogenesis, immunosuppression and metastasis. The design of nanocarriers capable of delivering therapeutic agents to specific cell populations has received considerable attention in the last decades. However, the capacity of many of these nanosystems to deliver multiple therapeutic agents with very different chemical properties is more limited. Herein, a novel multitasking nanoplatform capable of delivering large macromolecules and cytotoxic drugs to macrophages is presented. This novel nanosystem has exhibited excellent skills in performing simultaneous tasks, macrophage depletion and glucose starvation, maintaining the oxygen levels in the tissue. This nanodevice is composed of a dual-pore mesoporous silica core with the capacity to house small cytotoxic drugs, such as doxorubicin or zoledronic acid, and large macromolecules, such as glucose oxidase. The external surface of the silica core was coated with a lipid bilayer to avoid the premature release of the housed drugs. Finally, polymeric nanocapsules loaded with catalase were covalently anchored on the outer lipid bilayer, and carboxy-mannose was attached to the exposed side of the nanocapsules to provide selectivity to the macrophages. These nanoassemblies were able to transport enzymes (Gox and CAT), maintaining their catalytic activity. Therefore, they could induce glucose starvation, keeping the oxygen levels in the tissue, owing to the tandem enzymatic reaction. The capacity of these nanoassemblies to deliver therapeutic agents to macrophages was evaluated both in static and under flow conditions, showing a rapid capture of the nanoparticles by the macrophages. Once there, the nanoassemblies also exhibited excellent capacity to induce potent macrophage depletion. This strategy can be directly adapted for the treatment of different malignancies due to the modular nature of the nanoplatform, which can be loaded with different therapeutic agent combinations and pave the way for the development of personalized nanomedicines for diverse types of tumors.

In the process of tumor metastasis, tumor cells can acquire invasion by excessive uptake of nutrients and energy and interact with the host microenvironment to shape a premetastatic niche (PMN) that facilitates their colonization and progression in the distal sites. Pyruvate is an essential nutrient that engages in both energy metabolism and remodeling of the extracellular matrix (ECM) in the lungs for PMN formation, thus providing a target for tumor metastasis treatment. There is a paucity of strategies focusing on PMN prevention, which is key to metastasis inhibition. Here, we design a bioresponsive nanoparticle (HP/GU) based on a disulfide-cross-linked hyperbranched polyethylenimine (D-PEI) core and a hyaluronic acid (HA) shell with a reactive oxygen species (ROS)-sensitive cross-linker between them to encapsulate glucose oxidase (GOX) and a mitochondrial pyruvate carrier (MPC) inhibitor via electrostatic interaction, which reinforces starvation therapy and reduces PMN formation in the lungs via inhibiting pyruvate metabolism. In tumor cells, GOX and MPC inhibitors can be rapidly released and synergistically reduce the energy supply of tumor cells by consuming glucose and inhibiting pyruvate uptake to decrease tumor cell invasion. MPC inhibitors can also reduce ECM remodeling by blocking cellular pyruvate metabolism to prevent PMN formation. Consequently, HP/GU achieves an efficient inhibition of both primary and metastatic tumors and provides an innovative strategy for the treatment of tumor metastases.

Background: Salmonella Typhimurium poses a serious threat to human health worldwide, necessitating the development of a rapid, sensitive, and convenient method for S. Typhimurium detection. Nanozymes are considered ideal signal report elements, which are extensively used for developing colorimetric methods. However, single-component nanozymes display low catalytic activity, and colorimetric methods are susceptible to environmental interference, reducing the sensitivity and accuracy of detection results. To address these drawbacks, this study constructed a dual-mode composite nanozyme-based cascade colorimetric-fluorescence aptasensor for S. Typhimurium detection in food., Results: In this study, the composite Fe 3 O 4 @MIL-100(Fe) nanozymes were successful synthesized and demonstrated substantial peroxide-like activity, with 4.76-fold higher specificity activity (SA) than that of Fe 3 O 4 nanozymes. Then, a glucose oxidase (GOx)-Fe 3 O 4 @MIL-100(Fe) cascade reaction was developed for colorimetric detection via an aptamer to facilitate the formation of Fe 3 O 4 @MIL-100(Fe)/S. Typhimurium/carboxylated g-C 3 N 4 (CCN)-GOx sandwich complexes. Meanwhile, the fluorescence mode was achieved by measuring the fluorescence intensity of the sandwich complexes. In optimum conditions, the dual-mode detection limits (LOD) were 1.8 CFU/mL (colorimetric mode) and 1.2 CFU/mL (fluorescence mode), respectively, with the S. Typhimurium concentration ranging from 10 CFU/mL to 10 7  CFU/mL. Finally, the feasibility of the dual-mode colorimetric-fluorescence method was validated via three actual samples, yielding recovery rates of 77.32 % to91.17 % and 82.17 % to 103.7 %, respectively., Significance and Novelty: This study successfully develops a composite nanozyme-based cascade colorimetric and fluorescence dual-mode aptasensor for S. Typhimurium detection. It presents several distinct benefits, such as a broader linear range (10-10 7  CFU/mL), a lower LOD value (1.2 CFU/mL), and more accurate results. More importantly, the proposed dual-mode method displays a low LOD in colorimetric mode, demonstrating considerable potential for S. Typhimurium on-site detection in food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Recently, various techniques have been developed to accurately and sensitively detect tumor biomarkers for the early diagnosis and effective therapy of cancer. The electrochemiluminescence (ECL) method holding outstanding features including high sensitivity, ease of operation, and spatiotemporal controllability exhibited great potential for DNA/RNA detection, immunoassay, cancer cell detection, and environmental analysis. However, a glaring problem of ECL approaches is that the layer-by-layer modification on the electrode leads to poor stability and sensitivity of the sensors. Therefore, new simple and efficient methods for electrode modification which can effectively improve the ECL signal have attracted more and more research interests., Results: Based on the dual amplification strategy of target-induced CHA and nanocomposite probes leading to self-generated co-reactant (H 2 O 2 ), we proposed a highly sensitive miRNA-ECL detection system. The introduction of the target miRNA-21 triggers the CHA cycle amplification of DNA1 and biotin-modified DNA2, releasing the target miRNA-21 sequence for the target cycle reaction. After the reaction, the newly introduced DNA2 was combined with Au NPs modified with SA and Glucose oxidase (GOD). In the presence of oxygen, glucose was decomposed by GOD to produce H 2 O 2 , and then H 2 O 2 was immediately catalyzed by the Hemin/G-quadruplex at the double-stranded end of the CHA product to produce a large amount of O 2 -• . As a co-reactant of luminol, the ECL signal was significantly enhanced, thereby achieving highly sensitive detection of miRNA-21 content and obtaining a low detection limit of 0.65 fM. The high specificity of the ECL biosensor was also proved by base mismatch., Significance: Compared with other current detection methods, this sensor can achieve quantitative analysis of other target analytes by flexibly changing the probe DNA sequence, and provide a new feasible solution for the detection of tumor-associated markers. Benefiting from the improved sensitivity and selectivity, the proposed biosensing platform is expected to provide a new strategy for biomarkers analysis and outstanding prospect for further clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the in vitro motility assay (IVMA), actin filaments are observed while propelled by surface-adsorbed myosin motor fragments such as heavy meromyosin (HMM). In addition to fundamental studies, the IVMA is the basis for a range of lab-on-a-chip applications, e.g. transport of cargoes in nanofabricated channels in nanoseparation/biosensing or the solution of combinatorial mathematical problems in network-based biocomputation. In these applications, prolonged myosin function is critical as is the potential to repeatedly exchange experimental solutions without functional deterioration. We here elucidate key factors of importance in these regards. Our findings support a hypothesis that early deterioration in the IVMA is primarily due to oxygen entrance into in vitro motility assay flow cells. In the presence of a typically used oxygen scavenger mixture (glucose oxidase, glucose, and catalase), this leads to pH reduction by a glucose oxidase-catalyzed reaction between glucose and oxygen but also contributes to functional deterioration by other mechanisms. Our studies further demonstrate challenges associated with evaporation and loss of actin filaments with time. However, over 8 h at 21-26 °C, there is no significant surface desorption or denaturation of HMM if solutions are exchanged manually every 30 min. We arrive at an optimized protocol with repeated exchange of carefully degassed assay solution of 45 mM ionic strength, at 30 min intervals. This is sufficient to maintain the high-quality function in an IVMA over 8 h at 21-26 °C, provided that fresh actin filaments are re-supplied in connection with each assay solution exchange. Finally, we demonstrate adaptation to a microfluidic platform and identify challenges that remain to be solved for real lab-on-a-chip applications., (© 2024. The Author(s).)

CRISPR-Cas-based point-of-care testing (POCT) strategies have been widely explored for the detection of diverse biomarkers. However, these methods often require complicated operations, such as careful solution transfer steps, to achieve high sensitivity and accuracy. In this study, we combine a filter membrane-based POCT method with CRISPR-Cas12a for colorimetric detection of biomarkers. For the nucleic acid target, the trans-cleavage activity of CRISPR-Cas12a is directly triggered, cutting the single-stranded DNA linkers on glucose oxidase (GOx)-modified polymer nanoparticles. Due to the size difference between GOx and the polymer nanoparticles, GOx can be separated using a filter membrane. The filtrate containing GOx reacts with the substrate to generate a colorimetric signal. For the non-nucleic acid target, the non-nucleic acid signal is converted into a nucleic acid signal that activates CRISPR-Cas12a, resulting in a colorimetric signal. The entire operation is easy to perform, and the signal can be directly observed via the naked eye, which circumvents the use of costly instruments. The developed strategy holds great promise for accurate and accessible POCT detection of disease biomarkers in resource-limited settings.

A smartphone-mediated self-powered biosensor is fabricated for miRNA-141 detection based on the CRISPR/Cas12a cross-cutting technique and a highly efficient nanozyme. As a novel nanozyme and a signal-amplified coreaction accelerator, the AuPtPd@GDY nanozyme exhibits an excellent ability to catalyze cascade color reactions and high conductivity to enhance the electrochemical signal for miRNA-141 assays. After CRISPR/Cas12a cross-cutting of S2-glucose oxidase (S2-GOD), the electrochemical signal is weakened, and miRNA-141 is detected by monitoring the decrease in the signal. On the other hand, a cascade reaction among glucose, H 2 O 2 , and TMB is catalyzed by GOD and AuPtPd@GDY, respectively, resulting in a color change of the solution, which senses miRNA-141. The self-powered biosensor enables value-assisted and visual detection of miRNA-141 with limits of detection of 3.1 and 15 aM, respectively. Based on the dual-modal self-powered sensing system, a smartphone-mediated "all-in-one" biosensing chip is designed to achieve the real-time and intelligent monitoring of miRNA-141. This work provides a new approach to design multifunctional biosensors to realize the visualization and portable detection of tumor biomarkers.

The recognition of silver nanoparticles (AgNPs) as a nanozyme with peroxidase-like activity has offered a promising solution to address the challenges of bacterial resistance and argyria risk. However, the catalytic efficacy of AgNPs is limited by the need for a strong acidic environment and high concentrations of hydrogen peroxide (H 2 O 2 ). In this work, we developed a self-activated hydrogel cascade reactor (AUGP) for enhanced treatment of bacterial infection. The AUGP integrates the properties of glucose oxidase (GOx) and polyacrylamide (pAAm) hydrogel microsphere. The confinement effect of pAAm hydrogel microsphere enables glucose oxidation to occur in a confined space, which creates an acidic environment to activate AgNPs activity, initiating the cascade reaction between GOx and AgNPs. Meanwhile, the confinement effect facilitates the accumulation of a high local concentration of H 2 O 2 , allowing AUGP to generate hydroxyl radicals (•OH) without the need for external H 2 O 2 . Additionally, the release of Ag + from AUGP is achieved upon the generation of •OH. The synergistic action of Ag + and •OH confers exceptional antibacterial efficacy to AUGP. Importantly, the etching effect of H 2 O 2 ensures the absence of any residual AgNPs, reducing the risk of argyria. In vivo studies validated the efficacy of AUGP in wound disinfection with minimal toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we have for the first time constructed a ratiometric ECL biosensor for the ultrasensitive detection of microRNAs (miRNAs) using gold nanoparticles (Au NPs) to trigger both the low-potential emission from conjugated polymer poly(9,9-dioctylfluorene-2,7-diyl) dots (PFO Pdots) and the LSPR-ECL effect with sulfur-doped boron nitride quantum dots (S-BN QDs). PFO Pdots were first applied to the Au NPs-modified electrode, followed by covalent binding to capture the hairpin H1. Immediately thereafter, a small amount of miRNA-141 was able to generate a large amount of output DNA (OP) by traversing the target cycle. OP, H3-S-BN QDs, and H4-glucose oxidase (H4-GOD) were then added sequentially to the Au NPs-modified electrode surface, and the hybridization chain reaction (HCR) was initiated. This resulted in the introduction of a large amount of GOD into the system, which catalyzed the in situ formation of the co-reactant hydrogen peroxide (H 2 O 2 ) from the substrate glucose. Due to the electron transfer effect, the production of H 2 O 2 led to the ECL quenching of PFO Pdots. Meanwhile, H 2 O 2 served as a co-reactant of S-BN QDs, resulting in strong ECL emission of S-BN QDs at the cathode. Furthermore, the cathodic ECL intensity of S-BN QDs was further enhanced by an LSPR-ECL mechanism between Au NPs and S-BN QDs. By measuring the ratio of ECL intensities at two excitation potentials, this approach could provide sensitive and reliable detection of miRNA-141 in the range of 0.1 fM ∼10 nM, with a detection limit of 0.1 fM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Controlling glucose (Glu) intake is a "required course" for diabetics, thus quickly and precisely measuring the amount of Glu in food is crucial. For this purpose, a novel smartphone-assisted portable swab for the dual-mode visual detection of Glu was constructed combined the selectivity of natural enzymes with the controllable catalytic activity of nanozymes. Glu was specifically decomposed by glucose oxidase (natural enzyme) to produce H 2 O 2 , which was catalyzed by carbon dots (FeMn/N-CDs, nanozyme) to accelerate the reaction of o-phenylenediamine (OPD, colorless) to produce 2,3-diaminophenazine (DAP, yellow). As a result, the absorbance at 450 nm gradually increased with the increasing concentration of Glu, leading to a color change in the system from colorless to yellow. Meanwhile, the fluorescence of FeMn/N-CDs gradually decreased at 450 nm, while the fluorescence of DAP gradually increased at 550 nm, allowing for both ratiometric fluorescence and colorimetric dual-mode detection. Furthermore, natural enzyme and nanozyme together with OPD were co-loaded on the swabs to achieve cascade catalysis of Glu. The assembled portable swabs have detection ranges of 1-600 μM (LOD = 0.37 μM) and 4-1200 μM (LOD = 1.19 μM) for the colorimetric and fluorometric detection, respectively. The field test results on real samples demonstrated that the portable swabs have great promise for use in efficiently and accurately guiding the dietary intake of diabetics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bimetallic nanostructures are promising candidates for the development of enzyme-mimics, yet the deciphering of the structural impact on their catalytic properties poses significant challenges. By leveraging the structural versatility of nanocrystal aerogels, this study reports a precise control of Au-Pt bimetallic structures in three representative structural configurations, including segregated, alloy, and core-shell structures. Benefiting from a synergistic effect, these bimetallic aerogels demonstrate improved peroxidase- and glucose oxidase-like catalytic performances compared to their monometallic counterparts, unleashing tremendous potential in catalyzing the glucose cascade reaction. Notably, the segregated Au-Pt aerogel shows optimal catalytic activity, which is 2.80 and 3.35 times higher than that of the alloy and core-shell variants, respectively. This enhanced activity is attributed to the high-density Au-Pt interface boundaries within the segregated structure, which foster greater substrate affinity and superior catalytic efficiency. This work not only sheds light on the structure-property relationship of bimetallic catalysts but also broadens the application scope of aerogels in biosensing and biological detections., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Sensitive, reliable, and specific detection of microRNAs (miRNAs) is a key objective for disease diagnosis and prognosis. Here, a ratiometric fluorescent/electrochemiluminescent (FL/ECL) sensor was designed for the dual-mode detection of miRNA-122, a hepatocellular carcinoma biomarker. The strong ECL emission was achieved from imine-linked covalent organic framework (COF-LZU1) accelerator enriched Ru(bpy) 3 2+ molecules (Ru@COF-LZU1), which was applied as a delimited reaction micro-reactor to enhance ECL emission. Impressively, to construct an efficient sensing platform, self-feedback circuit was grafted at the vertex of DNA tetrahedral scaffold (DTS), which could provide a solution-phase-like environment and transform miRNA-122 into abundant single-stranded DNAs on the disposable electrode. Simultaneously, the carboxyfluorescein (FAM) tagged DNA segment was cleaved and released into the reaction solution, bringing in the recovery of FL response (FL on). Finally, the introduction of glucose oxidase (GOD) could generate H 2 O 2 by in situ catalyzing GOD to glucose, resulting in the decrease of ECL signal (ECL off). Relying on FL/ECL ratio value, miRNA-122 was quantified with high sensitivity, well selectivity, stability and favorable practicability, suggesting that the proposed biosensor hold great potential for clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aggravation of antibiotic resistance genes (ARGs) in the environment has posed a significant global health crisis. Accurate evaluation of ARGs levels in a facile manner is a pressing issue for environmental surveillance. Here, we demonstrate a unique dumbbell-shaped cascade nanozyme for visual/photoelectrochemical (PEC) dual-mode detection of ARGs. Gold nanoparticles (AuNPs) with tunable exposed facets are controllably anchored onto ZIF-8 dodecahedrons, exhibiting glucose oxidase (GOx)-like (ZIF-8@Au/G) and peroxidase (POD)-like (ZIF-8@Au/P) activities. Upon the occurrence of ARGs, an asymmetric cascade-amplified "dumbbell" configuration is spontaneously generated via target-induced DNA hybridization, comprising GOx-like ZIF-8@Au/G with capture DNA on one side and POD-like ZIF-8@Au/P with signal DNA on the opposite side. Such a cascade nano-system can efficiently oxidize colorless 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) into its green oxidation state and synergistically decompose H 2 O 2 , realizing colorimetric/PEC dual-mode ARGs detection with a detection limit of 0.112 nM. The applicability of the present bioassay is validated through measuring ARGs in real sludge samples. This work suggests the possibility to rationally design task-specific nanozymes and develop target-responsive nano-cascade assays for environmental monitoring., Competing Interests: Declaration of competing interest The authors declare that there is no interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Here, we report the preparation of a novel Janus nanoparticle with opposite Ir and mesoporous silica nanoparticles through a partial surface masking with toposelective modification method. This nanomaterial was employed to construct an enzyme-powered nanomachine with self-propulsion properties for on-command delivery. The cargo-loaded nanoparticle was provided with a pH-sensitive gate and unit control at the mesoporous face by first attaching boronic acid residues and further immobilization of glucose oxidase through reversible boronic acid esters with the carbohydrate residues of the glycoenzyme. Addition of glucose leads to the enzymatic production of H 2 O 2 and gluconic acid, being the first compound catalytically decomposed at the Ir nanoparticle face producing O 2 and causing the nanomachine propulsion. Gluconic acid leads to a pH reduction at the nanomachine microenvironment causing the disruption of the gating mechanism with the subsequent cargo release. This work demonstrates that enzyme-mediated self-propulsion improved release efficiency being this nanomotor successfully employed for the smart release of Doxorubicin in HeLa cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)