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1.
Anal Chim Acta ; 1312: 342761, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38834276

ABSTRACT

BACKGROUND: Diabetes is a significant health threat, with its prevalence and burden increasing worldwide indicating its challenge for global healthcare management. To decrease the disease severity, the diabetic patients are recommended to regularly check their blood glucose levels. The conventional finger-pricking test possesses some drawbacks, including painfulness and infection risk. Nowadays, smartphone has become a part of our lives offering an important benefit in self-health monitoring. Thus, non-invasive wearable sweat glucose sensor connected with a smartphone readout is of interest for real-time glucose detection. RESULTS: Wearable sweat glucose sensing device is fabricated for self-monitoring of diabetes. This device is designed as a body strap consisting of a sensing strip and a portable potentiostat connected with a smartphone readout via Bluetooth. The sensing strip is modified by carbon nanotubes (CNTs)-cellulose nanofibers (CNFs), followed by electrodeposition of Prussian blue. To preserve the activity of glucose oxidase (GOx) immobilized on the modified sensing strip, chitosan is coated on the top layer of the electrode strip. Herein, machine learning is implemented to correlate between the electrochemical results and the nanomaterial content along with deposition cycle of prussian blue, which provide the highest current response signal. The optimized regression models provide an insight, establishing a robust framework for design of high-performance glucose sensor. SIGNIFICANCE: This wearable glucose sensing device connected with a smartphone readout offers a user-friendly platform for real-time sweat glucose monitoring. This device provides a linear range of 0.1-1.5 mM with a detection limit of 0.1 mM that is sufficient enough for distinguishing between normal and diabetes patient with a cut-off level of 0.3 mM. This platform might be an alternative tool for improving health management for diabetes patients.


Subject(s)
Biosensing Techniques , Diabetes Mellitus , Machine Learning , Smartphone , Sweat , Wearable Electronic Devices , Humans , Sweat/chemistry , Biosensing Techniques/instrumentation , Diabetes Mellitus/diagnosis , Glucose/analysis , Nanotubes, Carbon/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Electrochemical Techniques/instrumentation
2.
Biosens Bioelectron ; 258: 116351, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38705074

ABSTRACT

Multifunctional single-atom catalysts (SACs) have been extensively investigated as outstanding signal amplifiers in bioanalysis field. Herein, a type of Fe single-atom catalysts with Fe-nitrogen coordination sites in nitrogen-doped carbon (Fe-N/C SACs) was synthesized and demonstrated to possess both catalase and peroxidase-like activity. Utilizing Fe-N/C SACs as dual signal amplifier, an efficient bipolar electrode (BPE)-based electrochemiluminescence (ECL) immunoassay was presented for determination of prostate-specific antigen (PSA). The cathode pole of the BPE-ECL platform modified with Fe-N/C SACs is served as the sensing side and luminol at the anode as signal output side. Fe-N/C SACs could catalyze decomposition of H2O2 via their high catalase-like activity and then increase the Faraday current, which can boost the ECL of luminol due to the electroneutrality in a closed BPE system. Meanwhile, in the presence of the target, glucose oxidase (GOx)-Au NPs-Ab2 was introduced through specific immunoreaction, which catalyzes the formation of H2O2. Subsequently, Fe-N/C SACs with peroxidase-like activity catalyze the reaction of H2O2 and 4-chloro-1-naphthol (4-CN) to generate insoluble precipitates, which hinders electron transfer and then inhibits the ECL at the anode. Thus, dual signal amplification of Fe-N/C SACs was achieved by increasing the initial ECL and inhibiting the ECL in the presence of target. The assay exhibits sensitive detection of PSA linearly from 1.0 pg/mL to 100 ng/mL with a detection limit of 0.62 pg/mL. The work demonstrated a new ECL enhancement strategy of SACs via BPE system and expands the application of SACs in bioanalysis field.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Electrodes , Hydrogen Peroxide , Iron , Limit of Detection , Luminescent Measurements , Luminol , Prostate-Specific Antigen , Catalysis , Luminescent Measurements/methods , Electrochemical Techniques/methods , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Humans , Luminol/chemistry , Prostate-Specific Antigen/analysis , Prostate-Specific Antigen/blood , Iron/chemistry , Glucose Oxidase/chemistry , Immunoassay/methods , Gold/chemistry , Peroxidase/chemistry , Metal Nanoparticles/chemistry , Nitrogen/chemistry , Carbon/chemistry , Naphthols
3.
Biosens Bioelectron ; 258: 116358, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38718634

ABSTRACT

Wearable sensors for sweat glucose monitoring are gaining massive interest as a patient-friendly and non-invasive way to manage diabetes. The present work offers an alternative on-body method employing an all-printed flexible electrochemical sensor to quantify the amount of glucose in human sweat. The working electrode of the glucose sensor was printed using a custom-formulated ink containing multi-walled carbon nanotube (MWCNT), poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOPT: PSS), and iron (II, III) oxide (Fe3O4) nanoparticles. This novel ink composition has good conductivity, enhanced catalytic activity, and excellent selectivity. The working electrode was modified using Prussian blue (PB) nanoparticles and glucose oxidase enzyme (GOx). The sensor displayed a linear chronoamperometric response to glucose from 1 µM to 400 µM, with a precise detection limit of ∼0.38 µM and an impressive sensitivity of ∼4.495 µAµM-1cm-2. The sensor stored at 4 °C exhibited excellent stability over 60 days, high selectivity, and greater reproducibility. The glucose detection via the standard addition method in human sweat samples acquired a high recovery rate of 96.0-98.6%. Examining human sweat during physical activity also attested to the biosensor's real-time viability. The results also show an impressive correlation between glucose levels obtained from a commercial blood glucose meter and sweat glucose concentrations. Remarkably, the present results outperform previously published printed glucose sensors in terms of detection range, low cost, ease of manufacturing, stability, selectivity, and wearability.


Subject(s)
Biosensing Techniques , Glucose Oxidase , Glucose , Limit of Detection , Nanocomposites , Nanotubes, Carbon , Sweat , Wearable Electronic Devices , Humans , Biosensing Techniques/instrumentation , Nanotubes, Carbon/chemistry , Sweat/chemistry , Nanocomposites/chemistry , Glucose/analysis , Glucose Oxidase/chemistry , Ink , Electrochemical Techniques , Ferric Compounds/chemistry , Ferrocyanides/chemistry , Polymers/chemistry , Reproducibility of Results , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Polystyrenes
4.
Chemphyschem ; 25(10): e202400460, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38778583

ABSTRACT

The front cover artwork is provided by Prof. Ron Naaman's group at the Weizmann Institute of Science. The image shows that direct electron transfer through GOx is governed by electron spins, which result from the chiral-induced spin selectivity (CISS) effect. Read the full text of the Research Article at 10.1002/cphc.202400033.


Subject(s)
Glucose Oxidase , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Electron Transport , Biocatalysis , Electrons
5.
Biosensors (Basel) ; 14(5)2024 May 13.
Article in English | MEDLINE | ID: mdl-38785717

ABSTRACT

Real-time monitoring of physiological indicators inside the body is pivotal for contemporary diagnostics and treatments. Implantable electrodes can not only track specific biomarkers but also facilitate therapeutic interventions. By modifying biometric components, implantable electrodes enable in situ metabolite detection in living tissues, notably beneficial in invasive glucose monitoring, which effectively alleviates the self-blood-glucose-managing burden for patients. However, the development of implantable electrochemical electrodes, especially multi-channel sensing devices, still faces challenges: (1) The complexity of direct preparation hinders functionalized or multi-parameter sensing on a small scale. (2) The fine structure of individual electrodes results in low spatial resolution for sensor functionalization. (3) There is limited conductivity due to simple device structures and weakly conductive electrode materials (such as silicon or polymers). To address these challenges, we developed multiple-channel electrochemical microneedle electrode arrays (MCEMEAs) via a separated functionalization and assembly process. Two-dimensional microneedle (2dMN)-based and one-dimensional microneedle (1dMN)-based electrodes were prepared by laser patterning, which were then modified as sensing electrodes by electrochemical deposition and glucose oxidase decoration to achieve separated functionalization and reduce mutual interference. The electrodes were then assembled into 2dMN- and 1dMN-based multi-channel electrochemical arrays (MCEAs), respectively, to avoid damaging functionalized coatings. In vitro and in vivo results demonstrated that the as-prepared MCEAs exhibit excellent transdermal capability, detection sensitivity, selectivity, and reproducibility, which was capable of real-time, in situ glucose concentration monitoring.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Electrodes , Animals , Glucose Oxidase , Rats , Humans , Blood Glucose/analysis , Needles
6.
ACS Sens ; 9(5): 2662-2672, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38689483

ABSTRACT

Dopamine (DA) signaling is critically important in striatal function, and this metabolically demanding process is fueled largely by glucose. However, DA and glucose are typically studied independently and, as such, the precise relationship between DA release and glucose availability remains unclear. Fast-scan cyclic voltammetry (FSCV) is commonly coupled with carbon-fiber microelectrodes to study DA transients. These microelectrodes can be modified with glucose oxidase (GOx) to generate microbiosensors capable of simultaneously quantifying real-time and physiologically relevant fluctuations of glucose, a nonelectrochemically active substrate, and DA, which is readily oxidized and reduced at the electrode surface. A chitosan hydrogel can be electrodeposited to entrap the oxidase enzyme on the sensor surface for stable, sensitive, and selective codetection of glucose and DA using FSCV. This strategy can also be used to entrap lactate oxidase on the carbon-fiber surface for codetection of lactate and DA. However, these custom probes are individually fabricated by hand, and performance is variable. This study characterizes the physical nature of the hydrogel and its effects on the acquired electrochemical data in the detection of glucose (2.6 mM) and DA (1 µM). The results demonstrate that the electrodeposition of the hydrogel membrane is improved using a linear potential sweep rather than a direct step to the target potential. Electrochemical impedance spectroscopy data relate information on the physical nature of the electrode/solution interface to the electrochemical performance of bare and enzyme-modified carbon-fiber microelectrodes. The electrodeposition waveform and scan rate were characterized for optimal membrane formation and performance. Finally, codetection of both DA/glucose and DA/lactate was demonstrated in intact rat striatum using probes fabricated according to the optimized protocol. Overall, this work improves the reliable fabrication of carbon-fiber microbiosensors for codetection of DA and important energetic substrates that are locally delivered to the recording site to meet metabolic demand.


Subject(s)
Biosensing Techniques , Carbon Fiber , Dopamine , Glucose Oxidase , Glucose , Microelectrodes , Dopamine/analysis , Glucose/analysis , Carbon Fiber/chemistry , Biosensing Techniques/methods , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Animals , Carbon/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Hydrogels/chemistry , Rats , Rats, Sprague-Dawley , Brain/metabolism , Chitosan/chemistry , Mixed Function Oxygenases/chemistry , Mixed Function Oxygenases/metabolism , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism
7.
Biomacromolecules ; 25(5): 3055-3062, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38693874

ABSTRACT

Polymersomes, nanosized polymeric vesicles, have attracted significant interest in the areas of artificial cells and nanomedicine. Given their size, their visualization via confocal microscopy techniques is often achieved through the physical incorporation of fluorescent dyes, which however present challenges due to potential leaching. A promising alternative is the incorporation of molecules with aggregation-induced emission (AIE) behavior that are capable of fluorescing exclusively in their assembled state. Here, we report on the use of AIE polymersomes as artificial organelles, which are capable of undertaking enzymatic reactions in vitro. The ability of our polymersome-based artificial organelles to provide additional functionality to living cells was evaluated by encapsulating catalytic enzymes such as a combination of glucose oxidase/horseradish peroxidase (GOx/HRP) or ß-galactosidase (ß-gal). Via the additional incorporation of a pyridinium functionality, not only the cellular uptake is improved at low concentrations but also our platform's potential to specifically target mitochondria expands.


Subject(s)
Glucose Oxidase , Horseradish Peroxidase , beta-Galactosidase , Glucose Oxidase/chemistry , Humans , beta-Galactosidase/chemistry , beta-Galactosidase/metabolism , Horseradish Peroxidase/chemistry , Horseradish Peroxidase/metabolism , Organelles/metabolism , Fluorescent Dyes/chemistry , Polymers/chemistry , Fluorescence , HeLa Cells , Mitochondria/metabolism
8.
Food Chem ; 453: 139623, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-38761730

ABSTRACT

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 (H2O2), and then HRP catalyzes H2O2 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.


Subject(s)
Capsicum , Food Contamination , Gold , Metal Nanoparticles , Ochratoxins , Ochratoxins/analysis , Gold/chemistry , Metal Nanoparticles/chemistry , Capsicum/chemistry , Capsicum/immunology , Food Contamination/analysis , Immunoenzyme Techniques/methods , Limit of Detection , Glucose Oxidase/chemistry , Single-Domain Antibodies/chemistry , Single-Domain Antibodies/immunology , Horseradish Peroxidase/chemistry , Biosensing Techniques
9.
Biosens Bioelectron ; 259: 116365, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38759309

ABSTRACT

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 Ag2O 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.


Subject(s)
Biosensing Techniques , Nanotubes, Carbon , Sutures , Wound Healing , Biosensing Techniques/instrumentation , Nanotubes, Carbon/chemistry , Humans , Glucose Oxidase/chemistry , Equipment Design , Bioelectric Energy Sources , Blood Glucose/analysis , Animals , Glucose/analysis , Glucose/isolation & purification , Carbon Fiber/chemistry
10.
J Colloid Interface Sci ; 670: 297-310, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38763026

ABSTRACT

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 (Mn+) 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 H2O2 conditions to generate carboxylic acids (R'COOH) and alcohols (R'OH) with reducibility, which will reduce M(n+1)+ to Mn+ and magnify the effect of CDT. Furthermore, glucose oxidase (GOx) was introduced to decompose glucose in tumor and generate H2O2 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 Fe3O4 and MoS2, 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.


Subject(s)
Hydrogen Peroxide , Hydrogen Peroxide/chemistry , Humans , Iron/chemistry , Liposomes/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Animals , Surface Properties , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Oxalates/chemistry , Mice , Particle Size , Cell Survival/drug effects
11.
Biosens Bioelectron ; 259: 116417, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38795496

ABSTRACT

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.


Subject(s)
Biosensing Techniques , Cyclic N-Oxides , Electrodes , Enzymes, Immobilized , Oxidation-Reduction , Polymerization , Biosensing Techniques/methods , Cyclic N-Oxides/chemistry , Enzymes, Immobilized/chemistry , Electrochemical Techniques/methods , Glucose/analysis , Glucose/chemistry , Glucose Oxidase/chemistry , Humans , Polymers/chemistry
12.
ACS Appl Mater Interfaces ; 16(21): 27668-27683, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38748922

ABSTRACT

Micro/nanomotors (MNMs) are miniature devices that can generate energy through chemical reactions or physical processes, utilizing this energy for movement. By virtue of their small size, self-propulsion, precise positioning within a small range, and ability to access microenvironments, MNMs have been applied in various fields including sensing, biomedical applications, and pollutant adsorption. However, the development of food-grade MNMs and their application in food delivery systems have been scarcely reported. Currently, there are various issues with the decomposition, oxidation, or inability to maintain the activity of some nutrients or bioactive substances, such as the limited application of curcumin (Cur) in food. Compared to traditional delivery systems, MNMs can adjust the transport speed and direction as needed, effectively protecting bioactive substances during delivery and achieving efficient transportation. Therefore, this study utilizes polysaccharides as the substrate, employing a simple, rapid, and pollution-free template method to prepare polysaccharide-based microtubes (PMTs) and polysaccharide-based micro/nanomotors (PMNMs). PMNMs can achieve multifunctional propulsion by modifying ferrosoferric oxide (Fe3O4), platinum (Pt), and glucose oxidase (GOx). Fe-PMNMs and Pt-PMNMs exhibit excellent photothermal conversion performance, showing promise for applications in photothermal therapy. Moreover, PMNMs can effectively deliver curcumin, achieving the effective delivery of nutrients and exerting the anti-inflammatory performance of the system.


Subject(s)
Curcumin , Polysaccharides , Curcumin/chemistry , Polysaccharides/chemistry , Animals , Mice , Platinum/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Ferrosoferric Oxide/chemistry , Humans , Food Ingredients/analysis
13.
Int J Biol Macromol ; 270(Pt 1): 132120, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38740153

ABSTRACT

A novel composite hydrogel was synthesized via Schiff base reaction between chitosan and di-functional poly(ethylene glycol) (DF-PEG), incorporating glucose oxidase (GOx) and cobalt metal-organic frameworks (Co-MOF). The resulting CS/PEG/GOx@Co-MOF composite hydrogel was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and energy-dispersive X-ray spectroscopy (EDS). The results confirmed successful integration and uniform distribution of Co-MOF within the hydrogel matrix. Functionally, the hydrogel exploits the catalytic decomposition of glucose by GOx to generate gluconic acid and hydrogen peroxide (H2O2), while Co-MOF gradually releases metal ions and protects GOx. This synergy enhanced the antibacterial activity of the composite hydrogel against both Gram-positive (S. aureus) and Gram-negative bacteria (E. coli), outperforming conventional chitosan-based hydrogels. The potential of the composite hydrogel in treating wound infections was evaluated through antibacterial and wound healing experiments. Overall, CS/PEG/GOx@Co-MOF hydrogel holds great promise for the treatment of wound infections, paving the way for further research and potential clinical applications.


Subject(s)
Anti-Bacterial Agents , Chitosan , Escherichia coli , Hydrogels , Metal-Organic Frameworks , Staphylococcus aureus , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Glucose Oxidase/chemistry , Animals , Cobalt/chemistry , Polyethylene Glycols/chemistry , Microbial Sensitivity Tests
14.
J Nanobiotechnology ; 22(1): 234, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724978

ABSTRACT

Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles "turned on" spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.


Subject(s)
Ferroptosis , Immunotherapy , Manganese Compounds , Membrane Proteins , Mice, Inbred BALB C , Nanoparticles , Nucleotidyltransferases , Oxides , Radiation-Sensitizing Agents , Animals , Mice , Immunotherapy/methods , Oxides/chemistry , Oxides/pharmacology , Female , Nucleotidyltransferases/metabolism , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Cell Line, Tumor , Nanoparticles/chemistry , Radiation-Sensitizing Agents/pharmacology , Radiation-Sensitizing Agents/chemistry , Membrane Proteins/metabolism , Ferroptosis/drug effects , Glucose Oxidase/metabolism , Reactive Oxygen Species/metabolism , Humans , DNA Damage , Tumor Microenvironment/drug effects
15.
J Colloid Interface Sci ; 666: 244-258, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38598997

ABSTRACT

Starvation therapy has shown promise as a cancer treatment, but its efficacy is often limited when used alone. In this work, a multifunctional nanoscale cascade enzyme system, named CaCO3@MnO2-NH2@GOx@PVP (CMGP), was fabricated for enhanced starvation/chemodynamic combination cancer therapy. CMGP is composed of CaCO3 nanoparticles wrapped in a MnO2 shell, with glucose oxidase (GOx) adsorbed and modified with polyvinylpyrrolidone (PVP). MnO2 decomposes H2O2 in cancer cells into O2, which enhances the efficiency of GOx-mediated starvation therapy. CaCO3 can be decomposed in the acidic cancer cell environment, causing Ca2+ overload in cancer cells and inhibiting mitochondrial metabolism. This synergizes with GOx to achieve more efficient starvation therapy. Additionally, the H2O2 and gluconic acid produced during glucose consumption by GOx are utilized by MnO2 with catalase-like activity to enhance O2 production and Mn2+ release. This process accelerates glucose consumption, reactive oxygen species (ROS) generation, and CaCO3 decomposition, promoting the Ca2+ release. CMGP can alleviate tumor hypoxia by cycling the enzymatic cascade reaction, which increases enzyme activity and combines with Ca2+ overload to achieve enhanced combined starvation/chemodynamic therapy. In vitro and in vivo studies demonstrate that CMGP has effective anticancer abilities and good biosafety. It represents a new strategy with great potential for combined cancer therapy.


Subject(s)
Calcium Carbonate , Glucose Oxidase , Manganese Compounds , Oxides , Glucose Oxidase/metabolism , Glucose Oxidase/chemistry , Glucose Oxidase/pharmacology , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Oxides/chemistry , Oxides/pharmacology , Humans , Animals , Calcium Carbonate/chemistry , Calcium Carbonate/pharmacology , Calcium Carbonate/metabolism , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Nanoparticles/chemistry , Povidone/chemistry , Povidone/pharmacology , Tumor Hypoxia/drug effects , Reactive Oxygen Species/metabolism , Cell Survival/drug effects , Particle Size , Cell Line, Tumor , Hydrogen Peroxide/metabolism , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Surface Properties , Mice, Inbred BALB C
16.
J Mater Chem B ; 12(16): 3996-4003, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38563677

ABSTRACT

Encapsulation of enzymes within porous materials has shown great promise for protecting enzymes from denaturation, increasing their tolerance to harsh environments and promoting their industrialization. However, controlling the conformational freedom of the encapsulated enzymes to enhance their catalytic performance remains a great challenge. To address this issue, herein, following immobilization of GOx and HRP on a thermo-responsive porous poly(styrene-maleic-anhydride-N-isopropylacrylamide) (PSMN) membrane, a GOx-HRP@PSMN@HZIF-8 composite was fabricated by encapsulating GOx-HRP@PSMN in hollow ZIF-8 (HZIF-8) with liposome (L) as the sacrificial template. The improved conformational freedom for enzymes arising from the hollow cavity formed in ZIF-8 through the removal of L enhanced the mass transfer and dramatically promoted the catalytic activity of the composite. Interestingly, at high temperature, the coiled PN moiety in PSMN provided the confinement effect for GOx-HRP, which also significantly boosted the catalytic performance of the composites. Compared to the maximum catalytic reaction rates (Vmax) of GOx-HRP@PSMN@LZIF-8, the free enzyme and GOx-HRP@ZIF-8, the Vmax of the GOx-HRP@PSMN@HZIF-8 composite exhibited an impressive 17.8-fold, 10.8-fold and 6.0-fold enhancement at 37 °C, respectively. The proposed composites successfully demonstrated their potential as catalytic platforms for the colorimetric detection of glucose in a cascade reaction. This study paves a new way for overcoming the current limitations of immobilizing enzymes in porous materials and the use of smart polymers for the potential fabrication of enzyme@polymer@MOF composites with tunable conformational freedom and confinement effect.


Subject(s)
Enzymes, Immobilized , Glucose Oxidase , Metal-Organic Frameworks , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Metal-Organic Frameworks/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Horseradish Peroxidase/chemistry , Horseradish Peroxidase/metabolism , Polymers/chemistry , Surface Properties , Porosity , Particle Size , Catalysis , Biocatalysis , Polystyrenes/chemistry
17.
J Colloid Interface Sci ; 665: 1065-1078, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38579389

ABSTRACT

Reactive oxygen species (ROS)-centered chemodynamic therapy (CDT) holds significant potential for tumor-specific treatment. However, insufficient endogenous H2O2 and extra glutathione within tumor microenvironment (TME) severely deteriorate the CDT's effectiveness. Herein, rich-Zn-Co3O4/N-doped porous carbon (Zn-Co3O4/NC) was fabricated by two-step pyrolysis, and applied to build high-efficiency nano-platform for synergistic cancer therapy upon combination with glucose oxidase (GOx), labeled Zn-Co3O4/NC-GOx for clarity. Specifically, the multiple enzyme-like activities of the Zn-Co3O4/NC were scrutinously investigated, including peroxidase-like activity to convert H2O2 to O2∙-, catalase-like activity to decompose H2O2 into O2, and oxidase-like activity to transform O2 to O2∙-, which achieved the CDT through the catalytic cascade reaction. Simultaneously, GOx reacted with intracellular glucose to produce gluconic acid and H2O2, realizing starvation therapy. In the acidic TME, the Zn-Co3O4/NC-GOx rapidly caused intracellular Zn2+ pool overload and disrupted cellular homeostasis for ion-intervention therapy. Additionally, the Zn-Co3O4/NC exhibited glutathione peroxidase-like activity, which consumed glutathione in tumor cells and reduced the ROS consumption for ferroptosis. The tumor treatments offer some constructive insights into the nanozyme-mediated catalytic medicine, coupled by avoiding the TME limitations.


Subject(s)
Cobalt , Hydrogen Peroxide , Neoplasms , Oxides , Humans , Porosity , Reactive Oxygen Species , Glucose Oxidase , Imidazoles , Carbon , Glutathione , Zinc , Neoplasms/drug therapy , Cell Line, Tumor , Tumor Microenvironment
18.
Nano Lett ; 24(15): 4682-4690, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38563501

ABSTRACT

Multienzyme assemblies mediated by multivalent interaction play a crucial role in cellular processes. However, the three-dimensional (3D) programming of an enzyme complex with defined enzyme activity in vitro remains unexplored, primarily owing to limitations in precisely controlling the spatial topological configuration. Herein, we introduce a nanoscale 3D enzyme assembly using a tetrahedral DNA framework (TDF), enabling the replication of spatial topological configuration and maintenance of an identical edge-to-edge distance akin to natural enzymes. Our results demonstrate that 3D nanoscale enzyme assemblies in both two-enzyme systems (glucose oxidase (GOx)/horseradish peroxidase (HRP)) and three-enzyme systems (amylglucosidase (AGO)/GOx/HRP) lead to enhanced cascade catalytic activity compared to the low-dimensional structure, resulting in ∼5.9- and ∼7.7-fold enhancements over homogeneous diffusional mixtures of free enzymes, respectively. Furthermore, we demonstrate the enzyme assemblies for the detection of the metabolism biomarkers creatinine and creatine, achieving a low limit of detection, high sensitivity, and broad detection range.


Subject(s)
Enzymes, Immobilized , Glucose Oxidase , Enzymes, Immobilized/chemistry , Horseradish Peroxidase/chemistry , Glucose Oxidase/chemistry , DNA/chemistry
19.
Nano Lett ; 24(15): 4691-4701, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38588212

ABSTRACT

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.


Subject(s)
Neoplasms , Tumor Microenvironment , Humans , Immunotherapy , Radioimmunotherapy , Glucose , Glucose Oxidase , Immunosuppressive Agents , Lactic Acid , Neoplasms/therapy , Cell Line, Tumor
20.
Talanta ; 274: 126042, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38583326

ABSTRACT

This work emphasizes the utilization of biochar, a renewable material, as an interesting platform for anchoring redox mediators and bioreceptors in the development of economic, environmentally friendly biosensors. In this context, Fe(III) ions were preconcentrated on highly functionalized activated biochar, allowing the stable synthesis of Prussian blue nanostructures with an average size of 58.3 nm. The determination of glucose was carried out by indirectly monitoring the hydrogen peroxide generated through the enzymatic reaction, followed by its subsequent redox reaction with reduced Prussian blue (also known as Prussian white) in a typical electrochemical-chemical mechanism. The EDC/NHS (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-Hydroxysuccinimide) pair was employed for the stable covalent immobilization of the enzyme on biochar. The biosensor demonstrated good enzyme-substrate affinity, as evidenced by the Michaelis-Menten apparent kinetic constant (4.16 mmol L-1), and analytical performance with a wide linear dynamic response range (0.05-5.0 mmol L-1), low limits of detection (0.94 µmol L-1) and quantification (3.13 µmol L-1). Additionally, reliable repeatability, reproducibility, stability, and selectivity were obtained for the detection of glucose in both real and spiked human saliva and blood serum samples.


Subject(s)
Biosensing Techniques , Charcoal , Ferrocyanides , Glucose , Nanostructures , Ferrocyanides/chemistry , Biosensing Techniques/methods , Nanostructures/chemistry , Charcoal/chemistry , Glucose/analysis , Glucose/chemistry , Humans , Enzymes, Immobilized/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Blood Glucose/analysis , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Limit of Detection
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