Search

Skin interstitial fluid (ISF) has emerged as a significant reservoir of biomarkers for disease diagnosis and prevention. Microneedle (MN) patches are regarded as an optimal platform for ISF extraction from the skin due to their non-invasive nature. However, challenges such as prolonged sampling durations and complex detection procedures impede timely metabolic analysis. In this investigation, we amalgamated MN technology with immobilized enzyme technology to fabricate a dual-layer MN patch integrating sampling and detection functionalities, thereby enabling in-situ colorimetric detection of hyperglycemia. The tip layer of the patch, comprising polyvinyl alcohol/carboxymethyl chitosan (PVA/CMCS) MN, was synthesized utilizing a chemical crosslinking approach for the first time, with glucose oxidase (GOx) being incorporated. The hydrophilicity of CMCS expedited the extraction process, facilitating the retrieval of approximately 10 mg of ISF within 10 min. The backing layer consisted of an immobilized polyvinyl alcohol-chitosan-horseradish peroxidase (PVA-CS-HRP) hydrogel film loaded with 3,3', 5,5'-tetramethylbenzidine (TMB). Incorporating macromolecular polymer PVA and CS for HRP immobilization addressed the issue of poor stability associated with traditional natural enzymes, thereby enhancing the sensitivity of the reaction system. The in-situ colorimetric sensor facilitated minimally invasive ISF extraction and swift conversion of glucose levels into detectable color changes., 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-promoted bacterial infection will seriously exacerbate diabetic wounds, and its current clinical treatments are suffering from the adverse effects associated with off-target, bacterial resistance, and glycemic fluctuation. Herein, we present a kind of glucose-fueled cationic nanomotors capable of remarkably enhancing antibacterial efficacy, and thus expediting diabetic wound healing. The nanomotors have positively charged surfaces, and consist of mesoporous bowl-shaped polydopamine nanoparticles grafted with quaternized polymer brushes and coupled with glucose oxidase (GOx) and catalase (CAT). Stemming from the GOx-CAT cascade reaction in diabetic wound microenvironment, they can perform robust chemotactic motion towards both high glucose regions, where bacteria proliferation predominantly occurs, and elevated H 2 O 2 levels, which bacterial metabolism produced. This enables the nanomotors to facilitate targeted migration towards bacteria-rich regions and simultaneous downregulation of glycemic levels, as well as to significantly enhance the electrostatic interaction between antibacterial components and bacteria. Consequently, the nanomotors exhibit amplified contact-killing effects of their attached cationic molecules, leading to an almost 10-fold enhancement in antibacterial efficacy compared to previous counterparts. The in vivo experiments approved that the nanomotors demonstrated the accelerated healing of infected diabetic wounds by S. aureus and biosafety. The results herein provide an insight into the clinical treatment of infected 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 paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Affected by persistent hyperglycemia, diabetic neuropathy, and vasculopathy hinder the progression of wound healing by exacerbating susceptibility to recurrent bacterial infection and impairing vascularization. In order to cater to the requirements of diabetic chronic wound healing at various stages, we designed an antibacterial and pro-angiogenic wound dressing with localized glucose-lowering capacity. In this study, we constructed a copper-based metal-organic framework (MOF) nanozyme and loaded with glucose oxidase (GOX) to prepare Cu-MOF/GOX, which was subsequently integrated with CS-Arg (chitosan modified by L-Arginine) and Pluronic (F127) to fabricate multifunctional Cu-MOF/GOX-Gel thermosensitive hydrogel. The GOX generated H 2 O 2 (hydrogen peroxide) and gluconic acid by consuming high blood glucose at the wound site, thus initiating an efficient antibacterial self-cascade catalytic in the initial stages of wound healing. With the further catalysis of in situ generated H 2 O 2 , NO (nitric oxide) was gradually released from the hydrogel, facilitating angiogenesis and accumulation of collagen, thereby expediting subsequent phases of wound healing. Overall, the Cu-MOF/GOX-Gel exhibits a comprehensive ability to locally regulate blood glucose levels, while also synergistically promoting antibacterial activity and angiogenesis, that effectively chronic diabetic wounds healing., 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.)

Crystallization degrades the physicochemical properties of honey and reduces consumer acceptance. To address this issue, radiofrequency was developed to investigate the decrystallization efficiency and quality impact mechanism of rape honey. The results showed that radiofrequency significantly decreased the number and size of crystals, leading to shortening the decrystallization time to less than 10 min. The response surface optimization methodology further indicated that the highest decrystallization rate (98.72 ± 0.34 %) and lower 5-Hydroxymethylfurfural (2.45 ± 0.12 mg/kg) contents were obtained. Furthermore, radiofrequency changed the honey from a pseudoplastic into a Newtonian fluid efficiently due to the volumetric heating feature. It is worth noting that the inactivation of glucose oxidase reduced the antibacterial capacity, while the increase in total phenolic and flavonoid contents improved the antioxidant capacity of rape honey. In summary, current findings indicated that radiofrequency is a potential alternative decrystallization technology for water baths., 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.)

The effectiveness of chemokinetic therapy nanozymes is severely constrained because of the low H 2 O 2 levels in the tumor microenvironment. Unlike other self-produced H 2 O 2 nanozymes, the N-CNTs-encapsulated CoNi alloy (CoNiCoNC) with glucose oxidase and lactate oxidase activities has two ways to produce H 2 O 2 . It can facilitate the transformation of glucose and lactic acid into H 2 O 2 simultaneously. First, the H 2 O 2 generation pathway is favorable for aggravating energy metabolism. Second, some produced H 2 O 2 can be decomposed by CoNiCoNC to H 2 O and O 2 with the 4e - pathway to alleviate the TME hypoxia. Third, H 2 O 2 can be catalyzed to form OH to enhance reactive oxygen species (ROS) content. Through proteomic analysis, nanozymes substantially impact the metabolic pathways of cancer cells because of their aggravating energy metabolism. The high levels of ROS can cause mitochondrial lipid peroxidation and cellular ferroptosis. Consequently, the two-way H 2 O 2 -selective nanoenzymatic platform realizes the synergistic effect of starvation therapy and chemokinetics., 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.)

Carbon dots (CQD) have received significant attention as a novel ratiometric fluorescent pH nanoprobe, owing to their favorable optical properties and excellent biocompatibility. Despite their appealing features, the precise mechanism behind the pH-sensitive photoluminescence of CQDs remains to be fully understood. This study endeavors to unravel the mechanism underlying the pH-responsive ratiometric fluorescence in dual-emission CQDs, synthesized through a one-step hydrothermal method using o-phenylenediamine and oxalic acid as precursors. The resultant CQDs exhibit inherent dual-emission at wavelengths of 383 nm and 566 nm, with the ratiometric fluorescence response tailored by the ratio of precursors, providing a robust tool for pH sensing across a range of 2 to 6. Detailed characterizations, including chemical, morphological, and optical analyses, alongside theoretical insights from time-dependent density functional theory (TD-DFT), elucidate the mechanism underlying the pH-dependent luminescence, attributed to the electron cloud transmission between amide and adjacent carboxyl groups on the CQD surface. The superior performance of these CQDs in real-time pH monitoring is demonstrated through their application in glucose oxidase-catalyzed reactions, showcasing their potential as efficient, reliable nanoprobes for biomedical research and diagnostic 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.)

Combination therapies have attracted significant attention because they address the limitations of monotherapy while improving overall efficacy. In this study, we designed a novel nanoplatform, named GOx@Fe-DMSN@PDA (GFDP), by integrating Fe 2+ into dendritic mesoporous silica nanoparticles (DMSN) and selecting glucose oxidase (GOx) as the model drug loaded into the DMSN pores. Additionally, we coated the surface of the DMSN with polydopamine (PDA) to confer pH/near infrared (NIR) light-responsive controlled-release behavior and photothermal therapy (PTT). The introduction of Fe 2+ into the DMSN framework greatly improved biodegradability and enhanced the peroxidase (POD)-like activity of GFDP. In addition, GOx could consume glucose and generate hydrogen peroxide (H 2 O 2 ) within tumor cells to facilitate starvation therapy and enhance cascade catalysis. The PDA coating provided the DMSN with an intelligent response release ability, promoting efficient photothermal conversion and achieving the PTT effect. Cellular tests showed that under NIR light irradiation, GFDP exhibited a synergistic effect of PTT-enhanced starvation therapy and cascade catalysis, with a half-maximal inhibitory concentration (IC 50 ) of 2.89 μg/mL, which was significantly lower than that of GFDP without NIR light irradiation (18.29 μg/mL). The in vivo anti-tumor effect indicated that GFDP could effectively accumulate at the tumor site for thermal imaging and showed remarkable synergistic therapeutic effects. In summary, GFDP is a promising nanoplatform for multi-modal combination therapy that integrates starvation therapy, PTT, and cascade catalysis., 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.)

A novel strategy that has emerged in recent years involves the use of aerogels for anti-inflammatory treatment, which has been extensively studied for its powerful application prospects in wound healing, diabetic complications, and tissue regeneration. However, the therapeutic efficacy of aerogels alone is compromised due to bacterial infections at the wound site. Therefore, it is necessary to incorporate effective antibacterial systems onto the aerogels to enhance their efficacy against bacterial infections. For instance, the design of cascade reactions targeting specific disease biomarkers for diagnostic and therapeutic purposes holds promise for enhancing treatment efficacy and precision. In this study, we successfully achieved the immobilization of glucose oxidase within an aerogel prepared from nanozymes, demonstrating remarkable catalytic activity and high-temperature stability. The cascade catalytic system comprising nanozymes and glucose oxidase was applied to combat Methicillin-resistant Staphylococcus aureus (MASR) bacterial infections, exhibiting effective biofilm removal capabilities. In therapeutic experiments on ulcerated wounds in diabetic mice, the cascade catalytic system demonstrated outstanding efficacy with excellent biocompatibility. The therapeutic effects were primarily manifested in the rapid clearance of biofilms formed by MASR, achieved by locally depleting glucose in the wound area, thereby promoting the healing process of ulcerated 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 paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Due to the current increase in the number of people suffering from diabetes worldwide, how to monitor the blood glucose level in the human body has become an urgent problem to be solved nowadays. The electrochemical sensor method can be used for real-time glucose monitoring due to its advantages of real-time monitoring capability and high sensitivity. Reduced graphene oxide (rGO) has great potential for application in the field of sensors due to its advantages of large specific surface area, high stability, and good electrical and thermal conductivity. Meanwhile, the synergistic effect between two-dimensional transition metal sulfides and graphene can improve the electrochemical performance of materials due to their similar mechanical flexibility and strength. This article uses flake graphite, copper sulfate, and glucose oxidase (GOx) as raw materials to prepare CuS/rGO/GOx/GCE electrodes, and explores the performance of electrode electrocatalysis for glucose. The results showed that the prepared sensor was characterized by a low detection limit (1.75 nM) and a wide linear range (0.1-100 mM) for glucose detection, displaying a good overall detection performance, and its sensing mechanism and dynamic process were also investigated. In addition, the sensor has outstanding selectivity, anti-interference, repeatability, reproducibility and practicality., 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.)

The controllable geometry and multifunctionality of DNA nano-bioreactors hold immense promise for disease diagnosis. Herein, a facile rolling circle amplification (RCA)-based crystallization method has been developed for highly efficient self-assembly of three-dimensional (3D) DNA nano-bioreactors, which show excellent cascade catalytic performance by confining bio-enzyme (glucose oxidase (GOx) used in this case) and copper ions (Cu 2+ ) in DNA nanoflowers (DNFs) structure. The participation of Cu 2+ during the self-assembly process not only endows the nano-bioreactors (designated as GOx/Cu@DNFs) with inspiring peroxidase-like activity but also greatly improves the assembly efficiency and yield via the effective coordination between Cu 2+ and RCA-generated long concatemeric DNAs. The integration of GOx and Cu 2+ in the constrained flower-like DNA nanomatrices makes for the efficient inter-catalyst communication, resulting in the striking enhancement of biocatalytic cascade activity. Based on the prepared nano-bioreactors, a colorimetric biosensor has been constructed for glucose detection, achieving a wide linear range (2-400 μM) and a low detection limit (0.45 μM). Furthermore, the proposed sensing strategy enables the accurate determination and discrimination of glucose levels in healthy and diabetic sera, delivering gratifying outcomes. Overall, the meticulously crafted cascade nano-bioreactors not only illuminate the design of multifunctional nanomaterials based on RCA, but also expand the conceptual framework of the universal analytical method for determining small molecules with catalytic reactions to generate H 2 O 2 ., 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-based electrochemical biosensors hold great promise for applications in health/disease monitoring, drug discovery, and environmental monitoring. However, inherently non-conductive nature of proteinaceous enzymes often hampers effective electron transfer at enzyme-electrode interface, limiting biosensor performance of enzyme bioelectrodes. To address this problem, we present an approach to synthesize polyaniline (PAN)-based conductive single enzyme nanocomposites of glucose oxidase (GOx) (denoted as PAN-GOx). To prevent multimerization of enzymes during nanocomposite synthesis and enable single enzyme wrapping, we activate GOx surface with phenylamine groups based on the programmed diffusion of reactants in the reaction solution. Subsequent in-situ polymerization enables the synthesis of nanoscale conductive PAN layer (∼2.7 nm thickness) grafted from individual GOx molecule. PAN-GOx retains 83% and 74% of its specific activity and catalytic efficiency, respectively, compared to free GOx, while demonstrating a ∼500% improved conductivity. Furthermore, PAN-GOx-based glucose biosensors show an approximately 16- and 3-fold higher sensitivity compared to biosensors prepared by using free GOx and a mixture of PAN and GOx, respectively. This study provides a facile method to fabricate conductive single enzyme nanocomposites with enhanced electron transfer, which can potentially be further modified and/or compounded with conductive materials for demonstrating high performance enzymatic bioelectrodes., 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.)

There is a significant clinical need to develop effective treatments for bone defects in patients with diabetes mellitus (DM), as they are at higher risk of fractures and impaired healing. Guided bone tissue engineering using biocompatible and biodegradable polymers is a promising approach. However, current diabetic bone regenerative therapies often fail due to the accumulation of advanced glycation products, which can affect the integration of traditional tissue engineering scaffolds with native bone. Therefore, novel approaches are needed to improve the efficacy of diabetic bone regeneration. This study presents a proof-of-concept development of a multifunctional polymer composite coating tailored towards restoring diabetes-related damage in osteoblast differentiation. Our composite system involves 3D-printed poly(caprolactone fumarate) (PCLF) and poly(caprolactone) (PCL) blend scaffolds coated with multifunctional chitosan methacrylate (chiMA). The chiMA coating is embedded with a sustained-release formulation of glucose oxidase (GOx) from MIL-127 metal-organic frameworks making the coating a stimuli-responsive biomolecule delivery system. The multifunctional coating is designed for the sustained release of GOx and sodium pyruvate for in vitro glucose modulation and oxidative stress reduction, respectively. We propose that sustained release of GOx from MIL-127 embedded chiMA coatings can modulate the high glucose (HG) cellular milieu towards normal glucose (NG), enhancing osteoblast (OB) differentiation via downstream effects. Our results show successful synthesis of MIL-127, encapsulation of GOx, and fabrication of composite coating on the PCLF/PCL scaffolds with effective enzyme activity measured as a function of lowering glucose concentration in HG media for 144 h to normal levels. In vitro evaluation of OB viability, attachment, proliferation, and differentiation showed an overall decrease in cellular activity in HG conditions, which was restored through the glucose-modulating functionality of the GOx-releasing MIL-127 coatings. Our results also presented preliminary evidence of a statistical correlation between DM-related gene markers and osteogenic markers in vitro that requires further exploration. Although this proof-of-concept study holds promise for advancing precision biomaterials development for diabetic tissue engineering and meeting the unmet clinical need for effective treatments and warrants future in vivo evaluation of the composite coating and molecular biology understanding of correlations between DM and osteogenic markers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benjamin D. Elder has reported that he has a relationship with SI-BONE Inc. that includes consulting or advisory work. Dr. Elder has consulting agreements with SI Bone and Depuy Synthes, receives clinical trial support from SI Bone and Stryker, is on the medical advisory board and has stock options in Injectsense, and also serves on the executive board of the International Society for Hydrocephalus and CSF Disorders. All other authors of this paper have confirmed that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To address the issue of high-dose treatment agents in magnetic hyperthermia-mediated multi-model tumor therapy, a unique iron-based theranostic nanoenzyme with excellent magnetothermal and catalytic properties was constructed. By using a high-temperature arc method, the iron carbon nanoparticles (MF1-3) with a particle size between 13.7 and 27.6 nm and shell thickness between 1 and 5 nm were prepared. After screening, we selected MF3 as the magnetic core due to its high Ms. value and excellent thermal properties. Under the magneto-photo dual thermal conditions, MF3 exhibited a remarkable specific absorption rate (SAR) of 4917 W/g, which was 20 times more than that of iron oxide. Notably, MF3 also exhibited best peroxidase (POD)-like catalytic in pH 5.0 and maintained stable catalytic performance at 45 °C. Considering the "starvation" strategy of cutting off the energy supply to tumor cells and killing them, the glucose oxidase (GOX) and chitosan oligosaccharide (COS) was further grafted onto MF3, forming the MF3/GOX/COS. This multifunctional therapeutic nanoenzyme not only exhibited significant peroxidase-like activity, but also had glucose decomposition and glutathione (GSH) consumption capabilities. The thermal effect significantly promoted the uptake of MF3/GOX/COS by 4T1 cells, and the IC 50 value of MF3/GOX/COS reached low to 3.75 μg/mL. In vivo anti-tumor experiment, compared with single treatment methods, the combined therapy of MF3/GOX/COS mediated magneto-photo thermotherapy (M-PTT) and starvation therapy (ST) exhibited higher tumor inhibition rate of 82.1 % by increased cell apoptosis through the mitochondrial pathway. Overall, MF3/GOX/COS therapeutic nanoenzyme combined the advantages of nano-catalysis, M-PTT and ST, providing a solution for achieving sustained, stable, and effective tumor inhibition rates at lower dose levels., Competing Interests: Declaration of competing interest We have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel smartphone-assisted fluorescent microfluidic-chip was designed for detecting sweat glucose. The microfluidic chip contained six microchambers, each of which was equipped with a glucose sensing membrane incorporating glucose oxidase (GOD), fluorescent O 2 probe PtTFPP and H 2 O 2 probe G1. Based upon O 2 consumption and H 2 O 2 generation during glucose catalysis by GOD, the chip produced two fluorescence signals towards glucose under single-wavelength excitation, i.e. green fluorescence in response to H 2 O 2 and red fluorescence to O 2 . The limit of detection (LOD) based on H 2 O 2 monitoring was 0.005 mM, while the LOD based on O 2 monitoring was 0.04 mM. Furthermore, the obtained chip was integrated with a smartphone-based portable platform to record RGB values for point-of-care testing of sweat glucose. Glucose calibration (Y = -3.45 + 1.81∗R + 0.68∗G) at 6-min time point was performed by combining R and G channels signals. The dual-monitoring analysis provided a more accurate and reliable verification of glucose detection. This smartphone-assistant optical microfluidic-chip device holds significant potential for portable self-management of glucose in personalized healthcare and 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.)

Self-powered biosensors with high sensitivity have garnered significant interest for their potential applications in the realm of portable sensing. Herein, a self-powered biosensor with a novel signal amplification strategy was developed by integrating target-controlled release of mediator with an enzyme biofuel cell for the ultrasensitive detection of acetamiprid (ACE). Zeolitic imidazolate framework-67 was utilized as both a nanocontainer for capturing the electron mediator 2,2'-azidobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and a precursor for the synthesis of cobalt nanoparticles/nitrogen, sulfur-codoped carbon nanotubes (Co NPs/NS-CNTs), which were employed as the electrode material for constructing both the glucose oxidase-based bioanode and the laccase-based biocathode. The target analyte ACE can specifically bind to its aptamer, leading to the release of ABTS, which cyclically participates in the catalytic reaction of the biocathode, thereby amplifying the electrochemical signal. By leveraging the benefits of ABTS cyclic catalysis and the effective electrocatalysis of bioelectrodes based on Co NPs/NS-CNTs, the self-powered biosensor has a broad detection range of 0.1-1000 fM and a low detection limit of 25 aM toward ACE. The proposed signal amplification approach presents a promising strategy for enhancing sensitivity and enabling portable analysis in applications of food safety, environmental monitoring, and medical diagnostics., 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.)

Transition metal-coordinated porphyrin metal-organic frameworks (MOFs) were perspective in photodynamic therapy (PDT) and catalytic therapy. However, the tumor hypoxia and the insufficient endogenous hydrogen peroxide (H 2 O 2 ) seriously limited their efficacies. Herein, by encapsulating ultrasmall iridium (Ir) and modifying glucose oxidase (GOx), an iron-coordinated porphyrin MOF (Fe-MOF) nanoplatform (Fe-MOF@Ir/GOx) was designed to strengthen PDT/catalytic therapy by producing reactive oxygen species (ROS) storm. In this nanoplatform, Fe-MOF showed glutathione (GSH)-responsive degradation, by which porphyrin, GOx and ultrasmall Ir were released. Moreover, ultrasmall Ir possessed dual-activities of catalase (CAT)-like and peroxidase (POD)-like, which provided sufficient oxygen (O 2 ) to enhance PDT efficacy, and hydroxyl radical (·OH) production was also improved by combining Fenton reaction of Fe 2+ . Further, GOx catalyzed endogenous glucose produced H 2 O 2 , also reduced pH value, which accelerated Fenton reaction and resulted in generation of ROS storm. Therefore, the developed Fe-MOF@Ir/GOx nanoplatform demonstrated enhanced PDT/catalytic therapy by producing ROS storm, and also provided a promising strategy to promote degradation/metabolism of inorganic nanoplatforms., 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.)

Ochratoxin A (OTA) in food poses a serious challenge to public health. Herein, using the nanobody-driven controllable aggregation of gold nanoparticles (AuNPs) in a glucose oxidase-tyramine-horseradish peroxidase (GOx-TYR-HRP) system, we propose a direct competitive plasmonic enzyme immunoassay (dc-PEIA) for OTA detection. The OTA-GOx conjugate catalyzes glucose to produce hydrogen peroxide (H 2 O 2 ), and then HRP catalyzes H 2 O 2 to generate hydroxyl radical which induces the crosslink of TYR. Crosslinked TYR leads to aggregation of AuNPs through strong electrostatic interactions, which is tunable based on the competition of OTA-GOx and free OTA for binding the immobilized nanobody. The optimized dc-PEIA achieves an instrumental limit of detection (LOD) of 0.275 ng/mL and a visual LOD of 1.56 ng/mL. It exhibits good selectivity for OTA and accuracy in the analysis of pepper samples, with the confirmation of high-performance liquid chromatography. Overall, the dc-PEIA is demonstrated as a useful tool for detecting OTA 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 Ltd. All rights reserved.)

The demetallation reaction of sulfanyl magnesium(II) porphyrazine with N-ethylphthalimide substituents, followed by remetallation with manganese(II) salts, yields the corresponding manganese(III) derivative (Pz3) with high efficiency. This novel manganese(III) sulfanyl porphyrazine was characterized by HPLC and analyzed using UV-Vis, MS, and FT-IR spectroscopy. Electrochemical experiments of Pz3 conducted in dichloromethane revealed electrochemical activity of the new complex due to both manganese and N-ethylphthalimide substituents redox transitions. Subsequently, Pz3 was deposited on multiwalled carbon nanotubes (MWCNTs), and this hybrid material was then applied to glassy carbon electrodes (GC). The resulting hybrid electroactive electrode material, combining manganese(III) porphyrazine with MWCNTs, showed a significant decrease in overpotential of H 2 O 2 oxidation compared to bare GC or GC electrodes modified with only carbon nanotubes (GC/MWCNTs). This improvement, attributed to the electrocatalytic performance of Mn 3+ , enabled linear response and sensitive detection of H 2 O 2 at neutral pH. Furthermore, a glucose oxidase (GOx)-containing biosensing platform was developed by modifying the prepared GC/MWCNT/Pz3 electrode for the electrochemical detection of glucose. The bioelectrode incorporating the newly designed Pz3 exhibited good activity in the presence of glucose, confirming effective electronic communication between the Pz3, GOx and MWCNT surface. The linear range for glucose detection was 0.2-3.7 mM.

Cascade-enzyme reaction systems have emerged as promising tools for treating malignant tumors by efficiently converting nutrients into toxic substances. However, the challenges of poor localized retention capacity and utilization of highly active enzymes often result in extratumoral toxicity and reduced therapeutic efficacy. In this study, we introduced a cell membrane-DNA nanoanchor (DNANA) with a spatially confined cascade enzyme for in vivo tumor therapy. The DNANAs are constructed using a polyvalent cholesterol-labeled DNA triangular prism, ensuring high stability in cell membrane attachment. Glucose oxidase (GOx) and horseradish peroxidase (HRP), both modified with streptavidin, are precisely confined to biotin-labeled DNANAs. Upon intratumoral injection, DNANA enzymes efficiently colonize the tumor site through cellular membrane engineering strategies, significantly reducing off-target enzyme leakage and the associated risks of extratumoral toxicity. Furthermore, DNANA enzymes demonstrated effective cancer therapy in vitro and in vivo by depleting glucose and producing highly cytotoxic hydroxyl radicals in the vicinity of tumor cells. This membrane-engineered cascade-enzyme reaction system presents a conceptual approach to tumor treatment.

Photothermal therapy (PTT) and photodynamic therapy (PDT) provide targeted approaches to cancer treatment, but each therapy has inherent limitations such as insufficient tissue penetration, uneven heat distribution, extreme hypoxia, and overexpressed HSP90 in tumor cells. To address these issues, herein, by encapsulating the IR780 dye and glucose oxidase (GOx) enzyme within ZIF-8 nanoparticles, we created a versatile system capable of combining photodynamic and enhanced photothermal therapy. The integration of the IR780 dye facilitated the generation of reactive oxygen species and hyperthermia upon light activation, enabling dual-mode cancer cell ablation. Moreover, GOx catalyzes the decomposition of glucose into gluconic acid and hydrogen peroxide, leading to the inhibition of ATP production and downregulation of heat shock protein 90 (HSP90) expression, sensitizing cancer cells to heat-induced cytotoxicity. This synergistic combination resulted in significantly improved therapeutic outcomes. Both in vitro and in vivo results validated that the nanoplatform demonstrated superior specificity and favorable therapeutic responses. Our innovative approach represents a promising strategy for overcoming current limitations in cancer treatments and offers the potential for clinical translation in the future.

High blood glucose and insufficient angiogenesis in diabetic wounds prevent healing, often leading to amputation or death. To address this, a multifunctional emulsion loaded with simvastatin and stabilized by enzymes was synthesized using ultrasound-assisted emulsification. This emulsion promotes angiogenesis and reduces blood glucose levels. Glucose oxidase and catalase at the emulsion interface catalyze a glucose cascading response, lowering the glucose concentration at the diabetic wound site and improving the wound microenvironment. Simvastatin in the emulsion further promotes angiogenesis. The emulsion significantly accelerated wound healing in diabetic rats, offering a promising approach to diabetic wound management.

The long-term operation feature of enzymatic biofuel cell-based self-powered biosensor (EBFC-SPB) endows them with the potential to execute dual-signal biosensing without having to integrate an extra signal acquisition device. Herein, cobalt and manganese codoped CeO 2 nanospheres (CoMn-CeO 2 NSs) with glucose-oxidase-like and peroxidase-like activities have been developed as substrate-switched dual-channel signal transduction components in EBFC-SPB for a dual-signal assay of aflatoxin B1 (AFB1). The CoMn-CeO 2 NSs modified with aptamer are anchored to a complementary DNA-attached bioanode of EBFC-SPB by base complementary pairing, which catalyze the glucose oxidation together with the glucose oxidase (GOx) on the bioanode. Once the AFB1 appears, CoMn-CeO 2 NSs will be released from the bioanode due to the binding specificity of the aptamer, resulting in a decreased catalytic efficiency and the first declining stage of EBFC-SPB. Accompanied by the introduction of H 2 O 2 , the residual CoMn-CeO 2 NSs on the bioanode switch to peroxidase-like activity and mediate the production of benzo-4-chlorohexadienone (4-CD) precipitate, which increases the steric hindrance and yields another declining stage of EBFC-SPB. By assessing the variation amplitudes during these two declining stages, the dual-signal assay of AFB1 has been realized with satisfying results. This work not only breaks ground in dual-signal bioassays but also deepens the application of nanozymes in EBFC-SPB.

Enzymes are known for their remarkable catalytic efficiency across a wide range of applications. Here, we present a novel and convenient nanoreactor platform based on zwitterionic polyelectrolyte complex vesicles (PCVs), assembled from oppositely charged homopoly(2-oxazoline)s, facilitating enzyme immobilization. We show remarkable enhancements in catalytic activity and stability by encapsulation of lipase as a model enzyme. Even as the temperature rises, the performance of the lipase remains robust. Further, the structural characteristics of PCVs, including hollow architecture and semipermeable membranes, endow them with unique advantages for enzyme cascade reactions involving glucose oxidase (GOx) and horseradish peroxidase (HRP). A decline in catalytic efficiency is shown when the enzymes are individually loaded and subsequently mixed, in contrast to the coloaded GOx-HRP-PCV group. We demonstrate that the vesicle structures establish confined environments where precise enzyme-substrate interactions facilitate enhanced catalytic efficiency. In addition, the nanoreactors exhibit excellent biocompatibility and efficient anti-tumor activity, which hold significant promise for biomedical applications within enzyme-based technologies.

Fenton/Fenton-like reaction induced chemical dynamic therapy (CDT) has been widely recognized in tumor therapy. Due to the low efficiency of conversion from high-valent metal ions (M ( n +1)+ ) to low-valent ions (M n + ) in the Fenton/Fenton-like catalytic process, enhancing the conversion efficiency safely and effectively would create a great opportunity for the clinical application of CDT. In the study, a universal nanoreactor (NR) consisting of liposome (Lip), tumor cell membrane (CM), and bis(2,4,5-trichloro-6-carboxyphenyl) oxalate (CPPO) is developed to tackle this challenge. The CPPO was first discovered to decompose under weak acidity and H 2 O 2 conditions to generate carboxylic acids (R'COOH) and alcohols (R'OH) with reducibility, which will reduce M ( n +1)+ to M n + and magnify the effect of CDT. Furthermore, glucose oxidase (GOx) was introduced to decompose glucose in tumor and generate H 2 O 2 and glucose acid, which promote the degradation of CPPO, further strengthening the efficiency of CDT, leading to a butterfly effect. This demonstrated that the butterfly effect triggered by NR and GOx encourages Fenton/Fenton-like reactions of Fe 3 O 4 and MoS 2 , thereby enhancing the tumor inhibition effect. The strategy of combining GOx and CPPO to strengthen the Fenton/Fenton-like reaction is a universal strategy, which provides a new and interesting perspective for CPPO in the application of CDT, reflecting the exquisite integration of Fenton chemistry and catalytic medicine., 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.)

Although cellular transport machinery is mostly ATP-driven and ATPase-dependent, there has been a recent surge in understanding colloidal transport processes relying on a nonspecific physical interaction with biologically significant small molecules. Herein, we probe the phoretic behavior of a biocolloid [composed of a Zn(II)-coordinated metallomicelle and enzymes horseradish peroxidase (HRP) and glucose oxidase (GOx)] when exposed to a concentration gradient of ATP under microfluidic conditions. Simultaneously, we demonstrate that an ATP-independent oxidative biocatalytic product formation zone can be modulated in the presence of a (glucose + ATP) gradient. We report that both directionality and extent of transport can be tuned by changing the concentration of the ATP gradient. This diffusiophoretic mobility of a submicrometer biocolloidal object for the spatial transposition of a biocatalytic zone signifies the ATP-mediated functional transportation without the involvement of ATPase. Additionally, the ability to analyze colloidal transport in microfluidic channels using an enzymatic fluorescent product-forming reaction could be a new nanobiotechnological tool for understanding transport and spatial catalytic patterning processes. We believe that this result will inspire further studies for the realization of elusive biological transport processes and target-specific delivery vehicles, considering the omnipresence of the ATP-gradient across the cell.

An ultrasensitive self-powered biosensor is constructed for miRNA-21 detection based on Au nanoparticles @ Pd nanorings (Au NPs@Pd NRs) and catalytic hairpin assembly (CHA). The Au NPs@Pd NRs possess excellent electrical conductivity to improve the electron transfer rate and show good elimination of byproduct H 2 O 2 to assist glucose oxidase (GOD) to catalyze glucose; CHA is used as an amplification strategy to effectively enhance the sensitivity of the biosensor. To further amplify the output signal, a capacitor is integrated into the self-powered biosensor. With multiple signal amplification strategies, the self-powered biosensor possesses a linear range of 0.1-10 -4 fM and a lower limit of detection (LOD) of 0.032 fM ( S / N = 3). In addition, the as-prepared self-powered biosensor displays potential applicability in the assay toward miRNA-21 in human serum samples.

A triple signal amplification strategy was integrated with a built-in double electrode and external energy storage device to fabricate a novel self-powered biosensor for ultrasensitive detection of miRNA-21. Specifically, DNA tetrahedra and haripin2-glucose oxidase are modified on the surface of the biocathode and bioanode by catalytic hairpin assembly (CHA) to achieve dual signal amplification. Moreover, triple signal amplification is realized by including an external capacitor. Consequently, the as-constructed self-powered biosensor demonstrates a low detection limit of 0.06 fM toward the miRNA-21 assay within the range of 0.1 fM to 10 pM. This study presents a practical and sensitive approach to timely cancer detection.

A new method of reducing the amount of reagent and sample for determination of thrombomodulin (TM) was developed based on competitive immunoreaction using a portable glucometer (PGM). Two types of nanocomposites, TM protein-modified magnetic nanoparticles (MNPs-TM) and TM antibody-/glucose oxidase-modified gold nanoparticles (Ab-GNPs-GOx), were prepared. Their binding product, MNPs-TM-Ab-GNPs-GOx, in the microvolumetric solution was used to catalyze the oxidation of glucose, leading to a decline of the glucose content. The TM-involved competitive immunoreaction had a negative effect on the generation of MNPs-/GNPs-based nanocomposites and inhibited the catalytic oxidation of glucose. The glucose content difference in the microvolumetric solution, which was revealed by a PGM, was in proportion to the logarithm of the TM concentration from 25 ng mL -1 to 2.5 μg mL -1 . The limit of detection was 5.7 ng mL -1 . Microvolumetric solution and a PGM were used in the measurement, which overcame some deficiencies of classical methods in chemo/biosensing, for example, special instrument, complicated measurement procedure, and high cost., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In nature, enzymatic pathways often involve compartmentalization effects that can modify the intrinsic activity and specificity of the different enzymes involved. Consequently, extensive research has focused on replicating and studying the compartmentalization effects on individual enzymes and on multistep enzyme "cascade" reactions. This study explores the influence of compartmentalization achieved using molecular crowding on the glucose oxidase/horseradish peroxidase (GOx/HRP) cascade reaction. The crowder tested is methoxy poly(ethylene glycol) (mPEG) that can, depending on conditions, promote GOx and HRP coassociation at the nanoscale and extend their contact time. Low-molecular-weight mPEG (0.35 kDa), but not mPEG of higher molecular weights (5 or 20 kDa), significantly enhanced the cascade reaction where up to a 20-fold increase in the rate of the cascade reaction was observed under some conditions. The combined analyses emphasize the particularity of low-molecular-weight mPEG and point toward mPEG-induced coassociation of HRP and GOx, producing nearest crowded neighbor effects of HRP on GOx, and vice versa . These altered the nanoscale environments of these enzymes, which influenced substrate affinity. Using mPEG to promote protein coassociation is simple and does not chemically modify the proteins studied. This approach could be of interest for more broadly characterizing nearest crowded neighbor effects (i.e., protein-protein interactions) for multiprotein systems (i.e., more than just two), thus making it an interesting tool for studying very complex systems, such as those found in nature.

Innovative signal amplification and transduction play pivotal roles in bioanalysis. Herein, cascading CRISPR/Cas and the nanozyme are integrated with electronic amplification in an organic photoelectrochemical transistor (OPECT) to enable triple signal amplification, which is exemplified by the miRNA-triggered CRISPR/Cas13a system and polyoxometalate nanozyme for OPECT detection of miRNA-21. The CRISPR/Cas13a-enabled release of glucose oxidase could synergize with peroxidase-like SiW 12 to induce catalytic precipitation on the photogate, inhibiting the interfacial mass transfer and thus the significant suppression of the channel current. The as-developed OPECT sensor demonstrates good sensitivity and selectivity for miRNA-21 detection, with a linear range from 1 fM to 10 nM and an ultralow detection limit of 0.53 fM. This study features the integration of bio- and nanoenzyme cascade and electronic triple signal amplification for OPECT detection.

Stable detection of diazinon (DZN) residues in vegetables is important for food safety. In this work, an electrochemiluminescence (ECL) aptasensor with dual-catalytic glucose in-situ production of H 2 O 2 was constructed for the stable detection of DZN in vegetables. Firstly, MWCNTs@MB was prepared using π-π stacking interactions between methylene blue (MB) and multi-walled carbon nanotubes (MWCNTs) to enhance the loading of MB on an electrode and thus catalyze the generation of H 2 O 2 from glucose. Secondly, Cu 2 O@AuNPs was formed by loading AuNPs on the surface of Cu 2 O through spontaneous reduction reaction, which improved the interfacial charge transfer, Cu 2 O nano-enzyme had glucose oxidase mimicking activity and could further catalyze the production of more H 2 O 2 from glucose. MWCNTs@MB and Cu 2 O@AuNPs played a key role in the in-situ generation of co-reacting reagent H 2 O 2 , which solved the problem of unstable detection caused by the easy decomposition of the H 2 O 2 solution added to the luminescence system. In addition, the aptamer was immobilized on the electrode surface by forming Au-S bonds with Cu 2 O@AuNPs. As a result, the ECL aptasensor performed good linearity in 1.00 pg mL -1 -1.00 μg mL -1 and a low limit of detection (LOD) to 0.39 pg mL -1 (S/N = 3). This work provided an effective method for the accurate and stable detection of DZN residues in vegetables, which was of great significance in ensuring food safety and assessing the environmental risk of DZN., 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 B.V.)

Based on CRISPR/Cas12a triggered ordered concatemeric DNA probes, a "on/off" self-powered biosensor is developed to achieve highly sensitive detection of thalassemia gene CD142 through open-circuit potential-assisted visual signal output. The ingeniously constructed glucose oxidase (GOD)-functionalized ordered concatemeric DNA probe structure can significantly amplify signal output, while the coupled CRISPR/Cas12a system is served as a "signal switch" with excellent signal-transducing capabilities. When the ordered concatemeric DNA probe structure is anchored on electrode, the response signal of the sensing system is in the "signal on" mode. While, the presence of the target activates the non-specific cleavage activity of the CRISPR/Cas12a system, causing the sensing system to switch to the "signal off" mode. In the detection system, GOD catalyzes the oxidation of glucose to produce hydrogen peroxide, which further catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to form a color product, enabling visual signal of the target through naked-eye color contrast. By employing a multifunctional analytical mode combining electrochemical and visual signal outputs, accurate determination of the target is achieved, with linear ranges of 0.0001-100 pM, and detection limits of 48.1 aM (S/N = 3). This work provides a reference method for sensitive detection of thalassemia genes and holds great diagnostic potential in biomedical 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.)

This study presents a modified screen-printed carbon electrode (SPCE) to determine glucose in a custom-built flow injection system. The biosensor was constructed by immobilizing glucose oxidase on porous platinum nanoparticles decorated on multi-walled carbon nanotubes (GOx@PPtNPs@MWCTNs). The fabrication of the biosensor was completed by coating the GOx@PPtNPs@MWCTNs nanocomposite on an SPCE modified with a nanocomposite of poly(3,4-ethylenedioxythiophene) and Prussian blue (GOx@PPtNPs@MWCTNs/PEDOT@PB/SPCE). The fabricated electrode accurately measured hydrogen peroxide (H 2 O 2 ), the byproduct of the GOx-catalyzed oxidation of glucose, and was then applied as a glucose biosensor. The glucose response was amperometrically determined from the PB-mediated reduction of H 2 O 2 at an applied potential of -0.10 V in a flow injection system. Under optimal conditions, the developed biosensor produced a linear range from 2.50 μM to 1.250 mM, a limit of detection of 2.50 μM, operational stability over 500 sample injections, and good selectivity. The proposed biosensor determined glucose in human plasma samples, achieving recoveries and results that agreed with the hexokinase-spectrophotometric method (P > 0.05). Combining the proposed biosensor with the custom-built sample feed, a portable potentiostat and a smartphone, enabled on-site glucose monitoring., 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.)

Mild photothermal therapy (PTT) is a spatiotemporally controllable method that utilizes the photothermal effect at relatively low temperatures (40-45 °C) to especially eliminate tumor tissues with negligible side effects on the surrounding normal tissues. However, the overexpression of heat shock protein 70 (HSP70) and limited effect of single treatment drastically impede the therapeutic efficacy. Herein, the constructed multifunctional core-shell structured Ag-Cu@SiO 2 -PDA/GOx nanoreactors (APG NRs) that provide a dual inhibition of HSP70 strategy for the second near-infrared photoacoustic (NIR-II PA) imaging-guided combined mild PTT/chemodynamic therapy (CDT). The Ag-Cu cores can convert endogenous H 2 O 2 to hydroxyl radical (•OH), which can induce lipid peroxidation (LPO) and further degrade HSP70. The polydopamine (PDA)/glucose oxidase (GOx) shells are utilized as the NIR-II photothermal agent to generate low temperature, and the GOx can reduce the energy supplies and inhibit energy-dependent HSP70 expression. Furthermore, both the generation of •OH and GOx-mediated energy shortage can reduce HSP70 expression to sensitize mild PTT under 1064 nm laser, and in turn, GOx and laser self-amplify the catalytic reactions of APG NRs for more production of •OH. The multifunctional nanoreactors will provide more potential possibilities for the clinical employment of mild PTT and the advancement of tumor combination therapies., (© 2024 Wiley‐VCH GmbH.)

Assembling functional molecules on the surface of an enzyme electrode is the most basic technique for constructing a biosensor. However, precise control of electron transfer interface or electron mediator on the electrode surface remains a challenge, which is a key step that affects the stability and sensitivity of enzyme-based biosensors. In this study, we propose the use of controllable free radical polymerization to grow stable 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) polymer as electron mediator on enzyme surface for the first time. Through scanning electron microscopy (SEM), Raman spectroscopy, electrode surface coverage measurement, static contact angle (SCA), and a series of electrochemical methods, it has been demonstrated that the TEMPO-based enzyme electrode exhibits a uniform hydrophilic morphology and stable electrochemical performance. Furthermore, the results show that the sensor demonstrates high sensitivity for detecting glucose biomolecules in artificial sweat and serum. Attributing to the quantitative and controllable radical polymerization of TEMPO redox assembled enzyme electrode surface, the as-proposed biosensor providing a use, storage, and inter-batch sensing stability, providing a vital platform for wearable/implantable biochemical sensors., Competing Interests: Declaration of competing interest There are no known conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This paper reports a flexible glucose biosensor which is modified by a reduced-swelling and conductive zwitterionic hydrogel enzyme membrane that contains two forms of chemical cross-links. One chemical cross-linking is induced by thermal initiators and forms the basal network of the hydrogel. Another cross-linking is achieved by the coordination interactions between the multivalent metal ion Al 3+ and anionic group -COO - of zwitterionic poly-carboxy betaine (pCBMA), which significantly increase the cross-linking density of the zwitterionic hydrogel, improving the reduced-swelling property and reducing the pore size. The better reduced-swelling property and reduced diameters of pores within the zwitterionic hydrogel make less glucose oxidase (GOx) leakage, thus significantly improving the enzyme membrane's service life. By introducing the Al 3+ and Cl - , the conductivity of the zwitterionic hydrogel is enhanced approximately 10.4-fold. According to the enhanced conductivity, the reduced-swelling property, and the high GOx loading capacity of the zwitterionic hydrogel, the sensitivity of the biosensor with GOx/pCBMA-Al 3+ is significantly improved by 5 times and has a long service life. Finally, the proposed GOx/pCBMA-Al 3+ biosensor was applied in non-invasive blood glucose detection on the human body, verifying the capability in practice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) is severely hindered by insufficient intracellular H 2 O 2 level that seriously deteriorates antitumor efficacy, albeit with its extensively experimental and theoretical research. Herein, we designed atomically dispersed FeCo dual active sites anchored in porous carbon polyhedra (termed FeCo/PCP), followed by loading with glucose oxidase (GOx) and anticancer doxorubicin (DOX), named FeCo/PCP-GOx-DOX, which converted glucose into toxic hydroxyl radicals. The loaded GOx can either decompose glucose to self-supply H 2 O 2 or provide fewer nutrients to feed the tumor cells. The as-prepared nanozyme exhibited the enhanced in vitro cytotoxicity at high glucose by contrast with those at less or even free of glucose, suggesting sufficient accumulation of H 2 O 2 and continual transformation to OH for CDT. Besides, the FeCo/PCP-GOx-DOX can subtly integrate starvation therapy, the FeCo/PCP-initiated CDT, and DOX-inducible chemotherapy (CT), greatly enhancing the therapeutic efficacy than each monotherapy., 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.)

Calcium overload can lead to tumor cell death. However, because of the powerful calcium channel excretory system within tumor cells, simplistic calcium overloads do not allow for an effective antitumor therapy. Hence, the nanoparticles are created with polyethylene glycol (PEG) donor-modified calcium phosphate (CaP)-coated, manganese-doped hollow mesopores Prussian blue (MMPB) encapsulating glucose oxidase (GOx), called GOx@MMPB@CaP-PEG (GMCP). GMCP with a three-mode enhancement of intratumor reactive oxygen species (ROS) levels is designed to increase the efficiency of the intracellular calcium overload in tumor cells to enhance its anticancer efficacy. The released exogenous Ca 2+ and the production of cytotoxic ROS resulting from the perfect circulation of the three-mode ROS outbreak generation that Fenton/Fenton-like reaction and consumption of glutathione from Fe 2+ /Fe 3+ and Mn 2+ /Mn 3+ circle, and amelioration of hypoxia from MMPB-guided and GOx-mediated starvation therapy. Photothermal efficacy-induced heat generation owing to MMPB accelerates the above reactions. Furthermore, abundant ROS contribute to damage to mitochondria, and the calcium channels of efflux Ca 2+ are inhibited, resulting in a calcium overload. Calcium overload further increases ROS levels and promotes apoptosis of tumor cells to achieve excellent therapy., (© 2024 Wiley‐VCH GmbH.)

Effective wound management has the potential to reduce both the duration and cost of wound healing. However, traditional methods often rely on direct observation or complex and expensive biological testing to monitor and evaluate the invasive damage caused by wound healing, which can be time-consuming. Biosensors offer the advantage of precise and real-time monitoring, but existing devices are not suitable for integration with sensitive wound tissue due to their external dimensions. Here, we have designed a self-powered biosensing suture (SPBS) based on biofuel cells to accurately monitor glucose concentration at the wound site and promote wound healing. The anode of the SPBS consists of carbon nanotubes-modified carbon fibers, tetrathiafulvalene (TTF), and glucose oxidase (GOx), while the cathode is composed of Ag 2 O and carbon nanotubes modified nanotubes modified carbon fibers. It was observed that SPBS exhibited excellent physical and chemical stability in vitro. Regardless of different bending degrees or pH values, the maximum power density of SPBS remained above 92%, which is conducive to long-term dynamic evaluation. Furthermore, the voltage generated by SPBS reflects blood glucose concentration, and measurements at wound sites are consistent with those obtained using a commercially available blood glucose meter. SPBS achieves the healing effect of traditional medical sutures after complete healing within 14 days. It offers valuable insights for intelligent devices dedicated to real-time wound monitoring., 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 B.V.)

A highly efficient ratiometric electrochemiluminescence (ECL) immunoassay was explored by bidirectionally regulating the ECL intensity of two luminophors. The immunoassay was conducted in a split-type mode consisting of an ECL detection procedure and a sandwich immunoreaction. The ECL detection was executed using a dual-disk glassy carbon electrode modified with two potential-resolved luminophors (g-C 3 N 4 -Ag and Ru-MOF-Ag nanocomposites), and the sandwich immunoreaction using glucose oxidase (GOx)-modified SiO 2 nanospheres as labels was carried out in a 96-well plate. The Ag nanoparticles (NPs) acted as bifunctional units both for triggering the resonance energy transfer (RET) with g-C 3 N 4 and for accelerating the electron transfer rate of the Ru-MOF-Ag ECL reaction. When the H 2 O 2 catalyzed by GOx in the 96-well plate was transferred to the dual-disk glass carbon electrode, the doped Ag NPs in the two luminophors could be etched, thus destroying the RET between C 3 N 4 and the accelerated reaction to Ru-MOF, resulting in an opposite trend in the ECL signal outputted from the dual disks. Using the ratio of the two signals for quantification, the constructed immunosensor for a model target, i.e. myoglobin, exhibited a low detection limit of 4.7 × 10 -14  g/mL. The ingenious combination of ECL ratiometry, bifunctional Ag NPs, and a split-type strategy effectively reduces environmental and human errors, offering a more precise and sensitive analysis for complex samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Cooked off-flavor was produced during the processing of concentrated peach puree (CPP), which led to aroma deterioration. Enzymatic treatment was beneficial in eliminating off-flavors and improving the aroma quality. Herein, the efficacy of glycosidase (AR2000), glucose oxidation (GOD), and their combination on the inhibition of off-flavors and aroma enhancement were evaluated. Compared with CPP, contents of benzaldehyde, benzyl alcohol, nonanal, and linalool increased by 198%, 1222%, 781%, and 71% after AR2000 treatment via the metabolisms of shikimate, glucose, linoleic acid, and linolenic acid, leading to the strengthening of floral and grassy. Due to the removal of 1-octen-3-one via linolenic acid metabolism, cooked off-flavor could be significantly weakened by GOD. Furthermore, Furthermore, the combination of AR2000 and GOD could not only inhibit the production of 1-octen-3-one to weaken the cooked note but also enhance grassy and floral attributes via the increase of aldehydes and alcohols., 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 © 2023. Published by Elsevier Ltd.)

To develop an amperometric flow-biosensor for glucose, the stabilizing effect of methylene blue (MB) toward adsorbed glucose oxidase (GOx) on carbon felt (CF) was successfully applied to prepare the GOx-modified CF-based enzyme reactor combined with a horseradish peroxidase (HRP)-modified CF-based H 2 O 2 detector. Upon mixing MB in the GOx-adsorption solution, the O 2 -dependent GOx-activity was significantly increased with increasing concentration of MB in the GOx-adsorption solution. The GOx-immobilization protocol on CF is very straightforward [ i.e. , adsorption of the GOx/MB mixed aqueous solution for 5 min under ultrasound (US)-irradiation]. Under the optimized operational conditions ( i.e. , applied potential, 0 vs. Ag/AgCl; carrier pH, 5.0; carrier flow rate, 4.0 mL min -1 ), the resulting GOx/MB-CF-reactor and HRP/TN-CF-detector combined amperometric flow-biosensor exhibited sensitive, selective, reproducible and stable cathodic peak current responses to glucose with the following analytical performances: sensitivity, 6.22 μA mM -1 ; linear range, 0.01 to 1 mM; limit of detection, 9.6 μM (S/N = 3, noise level, 20 nA); sample throughput, 46-96 samples per h for 10-0.1 mM glucose. The developed amperometric flow-biosensor allowed the determination of glucose in beverages and liquors, and the analytical results by the sensor were in fairly good agreement with those by conventional spectrophotometry.

Accurate diagnosis and classification of kidney cancer are crucial for high-quality healthcare services. However, the current diagnostic platforms remain challenges in the rapid and accurate analysis of large-scale clinical biosamples. Herein, we fabricated a bifunctional smart nanoplatform based on tannic acid-modified gold nanoflowers (TA@AuNFs), integrating nanozyme catalysis for colorimetric sensing and self-assembled nanoarray-assisted LDI-MS analysis. The TA@AuNFs presented peroxidase (POD)- and glucose oxidase-like activity owing to the abundant galloyl residues on the surface of AuNFs. Combined with the colorimetric assay, the TA@AuNF-based sensing nanoplatform was used to directly detect glucose in serum for kidney tumor diagnosis. On the other hand, TA@AuNFs could self-assemble into closely packed and homogeneous two-dimensional (2D) nanoarrays at liquid-liquid interfaces by using Fe 3+ as a mediator. The self-assembled TA@AuNFs (SA-TA@AuNFs) arrays were applied to assist the LDI-MS analysis of metabolites, exhibiting high ionization efficiency and excellent MS signal reproducibility. Based on the SA-TA@AuNF array-assisted LDI-MS platform, we successfully extracted metabolic fingerprints from urine samples, achieving early-stage diagnosis of kidney tumor, subtype classification, and discrimination of benign from malignant tumors. Taken together, our developed TA@AuNF-based bifunctional smart nanoplatform showed distinguished potential in clinical disease diagnosis, point-of-care testing, and biomarker discovery.

An innovative supramolecular architecture is reported for bienzymatic glucose biosensing based on the use of a nanohybrid made of multi-walled carbon nanotubes (MWCNTs) non-covalently functionalized with a Schiff base modified with two phenylboronic acid residues (SB-dBA) as platform for the site-specific immobilization of the glycoproteins glucose oxidase (GOx) and horseradish peroxidase (HRP). The analytical signal was obtained from amperometric experiments at - 0.050 V in the presence of 5.0 × 10 -4  M hydroquinone as redox mediator. The concentration of GOx and HRP and the interaction time between the enzymes and the nanohybrid MWCNT-SB-dBA deposited at glassy carbon electrodes (GCEs) were optimized through a central composite design (CCD)/response surface methodology (RSM). The optimal concentrations of GOx and HRP were 3.0 mg mL -1 and 1.50 mg mL -1 , respectively, while the optimum interaction time was 3.0 min. The bienzymatic biosensor presented a sensitivity of (24 ± 2) × 10 2 µA dL mg -1 ((44 ± 4) × 10 2 µA M -1 ), a linear range between 0.06 mg dL -1 and 21.6 mg dL -1 (3.1 µM-1.2 mM) (R 2  = 0.9991), and detection and quantification limits of 0.02 mg dL -1 (1.0 µM) and 0.06 mg dL -1 (3.1 µM), respectively. The reproducibility for five sensors prepared with the same MWCNT-SB-dBA nanohybrid was 6.3%, while the reproducibility for sensors prepared with five different nanohybrids and five electrodes each was 7.9%. The GCE/MWCNT-SB-dBA/GOx-HRP was successfully used for the quantification of glucose in artificial human urine and commercial human serum samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Nanofiber (NF) membrane systems that can provide cascade catalytic reaction and ferroptosis induction were developed for oral cancer therapy. Glucose oxidase (GOx) and aminoferrocene (AF) were introduced into the NF system for glucose deprivation/H 2 O 2 generation and OH radical generation, respectively. GOx offers starvation therapy and AF (including iron) provides chemodynamic therapy/ferroptosis for combating oral cancer. GOx (water-soluble) and AF (poorly water-soluble) molecules were successfully entrapped in the NF membrane via an electrospinning process. GOx and AF were incorporated into the polyvinyl alcohol (PVA)-based NF, resulting in PVA/GOx/AF NF with fast disintegration and immediate drug-release properties. In oral squamous cell carcinoma (YD-9 cells), the PVA/GOx/AF NF group exhibited higher cytotoxicity, antiproliferation potential, cellular ROS level, apoptosis induction, lipid ROS level, and malondialdehyde level compared to the other NF groups. The electrospun PVA/GOx/AF NF can be directly applied to oral cancer without causing pain, offering starvation/chemodynamic therapy and ferroptosis induction.

This study reports the development of a textile-based colaminar flow hybrid microbial-enzymatic biofuel cell. Shewanella MR-1 was used as a biocatalyst on the anode, and bienzymatic system catalysts based on glucose oxidase and horseradish peroxidase were applied on an air-breathing cathode to address the overpotential loss in a body-friendly way. A single-layer Y-shaped channel configuration with a double-inlet was adopted. Microchannels of biofuel cells were patterned by silk screen printing with Ecoflex to maintain the flexibility of textile substrates without harm to the human body. The electrodes were fabricated with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate and a mixture of multiwalled carbon nanotubes and single-walled carbon nanotubes by screen printing. The effects of electrode materials, catalyst type, catalyst concentration, and glucose concentration in the catholyte were investigated to optimize the fuel cell performance. The peak power density (44.9 μW cm -2 ) and maximum current density (388.9 μA cm -2 ) of the optimized hybrid biofuel cell were better than those of previously reported textile- or paper-substrate microscale single microbial fuel cells. The developed biofuel cell will be a useful platform as a microscale power source that is harmless to the environment and living organisms.

Effective continuous glucose monitoring solutions require consistent sensor performance over the lifetime of the device, a manageable variance between devices, and the capability of high volume, low cost production. Here we present a novel and microfabrication-compatible method of depositing and stabilizing enzyme layers on top of planar electrodes that can aid in the mass production of sensors while also improving their consistency. This work is focused on the fragile biorecognition layer as that has been a critical difficulty in the development of microfabricated sensors. We test this approach with glucose oxidase (GOx) and evaluate the sensor performance with amperometric measurements of in vitro glucose concentrations. Spincoating was used to deposit a uniform enzyme layer across a wafer, which was subsequently immobilized via glutaraldehyde vapor crosslinking and patterned via liftoff. This yielded an approximately 300 nm thick sensing layer which was applied to arrays of microfabricated platinum electrodes built on blank wafers. Taking advantage of their planar array format, measurements were then performed in high-throughput parallel instrumentation. Due to their thin structure, the coated electrodes exhibited subsecond stabilization times after the bias potential was applied. The deposited enzyme layers were measured to provide a sensitivity of 2.3 ± 0.2 μA mM -1 mm -2 with suitable saturation behavior and minimal performance shift observed over extended use. The same methodology was then demonstrated directly on top of wireless CMOS potentiostats to build a monolithic sensor with similar measured performance. This work demonstrates the effectiveness of the combination of spincoating and vapor stabilization processes for wafer scale enzymatic sensor functionalization and the potential for scalable fabrication of monolithic sensor-on-CMOS devices.

Mass transfer of bulky molecules, e.g ., bioenzymes, particularly for cross-scale multibiomolecules, imposes serious challenges for microporous metal-organic frameworks (MOFs). Here, we create a hierarchically porous MOF heterostructure featuring highly region-ordered micro-, meso-, and macro-pores by growing a microporous ZIF-8 shell onto a hollow Prussian blue core through an epitaxial growth strategy. This allows for localized loading of large bioenzyme glucose oxidase (GOx) and small drug 5-fluorouracil (5-FU) within specific pores simultaneously and triggers unique guest-carrier cooperative anticancer capabilities. The stable ZIF-8 outer layer effectively blocks the core pores, preventing the undesired leakage of GOx into normal tissues. The acidity-induced ZIF-8 degradation gradually releases Zn 2+ and loaded 5-FU for chemotherapy under acidic tumor microenvironments. With the loss of the shielding effect of the ZIF-8 coating, the released GOx depletes intratumoral glucose (Glu) for starvation therapy. Notably, an accelerated cascade reaction occurs between ZIF-8 decomposition and GOx release, facilitated by the modulator factor of Glu. This culminates in the realization of synergistic cancer therapy, as comprehensively demonstrated by in vitro and in vivo experiments, as well as transcriptome sequencing analyses. Our work not only introduces a hierarchically porous MOF heterostructure with highly region-ordered pores but also provides a perspective for guest-carrier cooperative anticancer therapy.

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-NC etch /SAC) bimetallic peroxidase mimetic enzyme with abundant active sites etched by H 2 O 2 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, H 2 O 2 was generated by substrate catalysis via secondary antibody-labeled glucose oxidase (GOx), while FeMn-NC etch /SAC nanozymes catalyzed the decomposition of H 2 O 2 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.

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell-cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu 2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H 2 O 2 ) catalyzed by intracellular GOx into oxygen (O 2 ), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery., (© 2024. The Author(s).)