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1.
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
2.
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
3.
Int J Biol Macromol ; 268(Pt 1): 131870, 2024 May.
Article in English | MEDLINE | ID: mdl-38670199

ABSTRACT

As one of the most important industrial enzymes, α-amylase is widely used in food processing, such as starch sugar and fermentation, bringing high added value to industry of more than a trillion dollars. We developed a multi-enzyme system (Glu&Gox@Cu-MOF-74) prepared by embedding α-glucosidase (Glu) and glucose oxidase (Gox) into the biomimetic metal-organic framework Cu-MOF-74 using in situ encapsulation within 15 min at room temperature for efficient and sensitive detection of α-amylase activity. Benefitting from the remarkable peroxidase-mimicking property and rigid skeleton of Cu-MOF-74, the biocatalytic platform exhibited excellent cascade activity and tolerance in various extremely harsh environments compared to natural enzymes. On this basis, a cascade biocatalytic platform was constructed for the detection of α-amylase activity with wide linear range (5-100 U/L) and low limit of detection (1.45 U/L). The colorimetric cascade scheme is important for the sensitive and selective determination of α-amylase in complex fermentation samples, and the detection time is short (∼0.5 h). This work provides new ideas for the detection of α-amylase based on the cascade amplification method.


Subject(s)
Glucose Oxidase , Metal-Organic Frameworks , alpha-Amylases , alpha-Amylases/analysis , alpha-Amylases/metabolism , alpha-Amylases/chemistry , Metal-Organic Frameworks/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Biosensing Techniques/methods , Colorimetry/methods , alpha-Glucosidases/metabolism , alpha-Glucosidases/analysis , Biocatalysis , Copper/chemistry , Copper/analysis , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Limit of Detection
4.
Bioprocess Biosyst Eng ; 47(6): 919-929, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38644439

ABSTRACT

The growing need in the current market for innovative solutions to obtain lactose-free (L-F) milk is caused by the annual increase in the prevalence of lactose intolerance inside as well as the newborn, children, and adults. Various configurations of enzymes can yield two distinct L-F products: sweet (ß-galactosidase) and unsweet (ß-galactosidase and glucose oxidase) L-F milk. In addition, the reduction of sweetness through glucose decomposition should be performed in a one-pot mode with catalase to eliminate product inhibition caused by H2O2. Both L-F products enjoy popularity among a rapidly expanding group of consumers. Although enzyme immobilization techniques are well known in industrial processes, new carriers and economic strategies are still being searched. Polymeric carriers, due to the variety of functional groups and non-toxicity, are attractive propositions for individual and co-immobilization of food enzymes. In the presented work, two strategies (with free and immobilized enzymes; ß-galactosidase NOLA, glucose oxidase from Aspergillus niger, and catalase from Serratia sp.) for obtaining sweet and unsweet L-F milk under low-temperature conditions were proposed. For free enzymes, achieving the critical assumption, lactose hydrolysis and glucose decomposition occurred after 1 and 4.3 h, respectively. The tested catalytic membranes were created on regenerated cellulose and polyamide. In both cases, the time required for lactose and glucose bioconversion was extended compared to free enzymes. However, these preparations could be reused for up to five (ß-galactosidase) and ten cycles (glucose oxidase with catalase).


Subject(s)
Enzymes, Immobilized , Glucose Oxidase , Lactose , Milk , beta-Galactosidase , beta-Galactosidase/metabolism , beta-Galactosidase/chemistry , Milk/chemistry , Lactose/metabolism , Lactose/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Animals , Aspergillus niger/enzymology , Glucose/metabolism , Glucose/chemistry , Catalase/metabolism , Catalase/chemistry , Membranes, Artificial
5.
Nat Commun ; 15(1): 3440, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38653977

ABSTRACT

Oxidative stress from excess H2O2 activates transcription factors that restore redox balance and repair oxidative damage. Although many transcription factors are activated by H2O2, it is unclear whether they are activated at the same H2O2 concentration, or time. Dose-dependent activation is likely as oxidative stress is not a singular state and exhibits dose-dependent outcomes including cell-cycle arrest and cell death. Here, we show that transcription factor activation is both dose-dependent and coordinated over time. Low levels of H2O2 activate p53, NRF2 and JUN. Yet under high H2O2, these transcription factors are repressed, and FOXO1, NF-κB, and NFAT1 are activated. Time-lapse imaging revealed that the order in which these two groups of transcription factors are activated depends on whether H2O2 is administered acutely by bolus addition, or continuously through the glucose oxidase enzyme. Finally, we provide evidence that 2-Cys peroxiredoxins control which group of transcription factors are activated.


Subject(s)
Hydrogen Peroxide , Oxidative Stress , Transcription Factors , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/pharmacology , Oxidative Stress/drug effects , Transcription Factors/metabolism , Transcription Factors/genetics , Humans , Peroxiredoxins/metabolism , Peroxiredoxins/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , NF-kappa B/metabolism , Forkhead Box Protein O1/metabolism , Forkhead Box Protein O1/genetics , NFATC Transcription Factors/metabolism , Glucose Oxidase/metabolism , Animals
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 315: 124269, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38608561

ABSTRACT

A colorimetric immunoassay was built for determination of carcinoembryonic antigen (CEA) based on papain-based colorimetric catalytic sensing system through the use of glucose oxidase (GOx). In the presence of GOx, glucose was catalytically oxidized to produce H2O2. Through the assistance of papain (as a peroxide mimetic enzyme), the signal came from the oxidative color development of 3,3',5,5'-tetramethylbenzidine (TMB, from colorless to blue) catalyzed by the generated H2O2. Herein, a sandwich-type immunoassay was built based on GOx as labels. As the concentration of CEA increased, more GOx-labeled antibodies specifically associate with target, which leaded to more H2O2 generation. Immediately following this, more TMB were oxidized with the addition of papain. Accordingly, the absorbance increased further. As a result, the concentration of CEA is positively correlated with the change in absorbance of the solution. Under optimal conditions, the CEA concentration was linear in the range of 0.05-20.0 ng/mL, and the limit of detection (LOD) reached 37 pg/mL. The papain-based colorimetric immunoassay also exhibited satisfactory repeatability, stability, and selectivity.


Subject(s)
Carcinoembryonic Antigen , Colorimetry , Limit of Detection , Papain , Carcinoembryonic Antigen/analysis , Colorimetry/methods , Papain/metabolism , Immunoassay/methods , Humans , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Hydrogen Peroxide/chemistry , Catalysis , Benzidines/chemistry , Biosensing Techniques/methods , Reproducibility of Results
7.
Talanta ; 274: 126010, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38569372

ABSTRACT

Intracellular glucose detection is crucial due to its pivotal role in metabolism and various physiological processes. Precise glucose monitoring holds significance in diabetes management, metabolic studies, and biotechnological applications. In this study, we developed an innovative and expedient cell-permeable nanoreactor for intracellular glucose based on surface-enhanced Raman scattering (SERS). The nanoreactor was designed with gold nanoparticles (AuNPs), which were engineered with glucose oxide (GOx) and a H2O2-responsive Raman reporter 2-mercaptohydroquinone (2-MHQ). The interaction between 2-MHQ and H2O2 generated by glucose and GOx could simultaneously induce the appearance in the peak at 985 cm-1. Our results showed excellent performance in detecting glucose within the concentration range from 0.1 µM to 10 mM, with a low detection limitation of 14.72 nM. In addition, the glucose distribution in single HeLa cells was evaluated by real time SERS mapping. By combining noble metal particles and natural oxidases, the nanoreactor possesses both Raman activity and enzymatic functionality, thus enables sensitive glucose detection and facilitates imaging at a single cell level, which offers an insightful monitoring of cellular processes.


Subject(s)
Glucose , Gold , Metal Nanoparticles , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Humans , HeLa Cells , Gold/chemistry , Metal Nanoparticles/chemistry , Glucose/analysis , Glucose/metabolism , Hydrogen Peroxide/analysis , Hydrogen Peroxide/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism
8.
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
9.
Analyst ; 149(9): 2756-2761, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38563766

ABSTRACT

New dynamic, wireless and cost-effective analytical devices are developing rapidly in biochemical analysis. Here, we report on a remotely-controlled rotating electrochemiluminescence (ECL) sensing system for enzymatic detection of a model analyte, glucose, on both polarized sides of an iron wire acting as a bipolar electrode. The iron wire is controlled by double contactless mode, involving remote electric field polarization, and magnetic field-induced rotational motion. The former triggers the interfacial polarization of both extremities of the wire by bipolar electrochemistry, which generates ECL emission of the luminol derivative (L-012) with the enzymatically produced hydrogen peroxide in presence of glucose, at both anodic and cathodic poles, simultaneously. The latter generates a convective flow, leading to an increase in mass transfer and amplifying the corresponding ECL signals. Quantitative glucose detection in human serum samples is achieved. The ECL signals were found to be a linear function of the glucose concentration within the range of 10-1000 µM and with a limit of detection of 10 µM. The dynamic bipolar ECL system simultaneously generates light emissions at both anodic and cathodic poles for glucose detection, which can be further applied to biosensing and imaging in autonomous devices.


Subject(s)
Electrochemical Techniques , Luminescent Measurements , Luminescent Measurements/methods , Humans , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Electrodes , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Limit of Detection , Blood Glucose/analysis , Wireless Technology , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Luminol/chemistry
10.
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
11.
Lab Chip ; 24(9): 2454-2467, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38644805

ABSTRACT

Safe, accurate, and reliable analysis of urinary biomarkers is clinically important for early detection and monitoring of the progression of chronic kidney disease (CKD), as it has become one of the world's most prevalent non-communicable diseases. However, current technologies for measuring urinary biomarkers are either time-consuming and limited to well-equipped hospitals or lack the necessary sensitivity for quantitative analysis and post a health risk to frontline practitioners. Here we report a robust paper-based dual functional biosensor, which is integrated with the clinical urine sampling vial, for the simultaneous and quantitative analysis of pH and glucose in urine. The pH sensor was fabricated by electrochemically depositing IrOx onto a paper substrate using optimised parameters, which enabled an ultrahigh sensitivity of 71.58 mV pH-1. Glucose oxidase (GOx) was used in combination with an electrochemically deposited Prussian blue layer for the detection of glucose, and its performance was enhanced by gold nanoparticles (AuNPs), chitosan, and graphite composites, achieving a sensitivity of 1.5 µA mM-1. This dual function biosensor was validated using clinical urine samples, where a correlation coefficient of 0.96 for pH and 0.98 for glucose detection was achieved with commercial methods as references. More importantly, the urine sampling vial was kept sealed throughout the sample-to-result process, which minimised the health risk to frontline practitioners and simplified the diagnostic procedures. This diagnostic platform, therefore, holds high promise as a rapid, accurate, safe, and user-friendly point-of-care (POC) technology for the analysis of urinary biomarkers in frontline clinical settings.


Subject(s)
Biosensing Techniques , Paper , Point-of-Care Systems , Humans , Hydrogen-Ion Concentration , Gold/chemistry , Glucose/analysis , Urinalysis/instrumentation , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Electrochemical Techniques , Metal Nanoparticles/chemistry , Graphite/chemistry , Biomarkers/urine
12.
Mater Horiz ; 11(10): 2406-2419, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38440840

ABSTRACT

Enzymes provide a class of potential options to treat cancer, while the precise regulation of enzyme activities for effective and safe therapeutic actions has been poorly reported. Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared (NIR-II) photoactivatable ferroptosis-immunotherapy are reported in this study. Such nanoagents (termed SPHGA) consist of hemoglobin (Hb)-based semiconducting polymer (SP@Hb), adenosine deaminase (ADA) and glucose oxidase (GOx) with loadings in a thermal-responsive nanoparticle shell. NIR-II photoactivation of SPHGA results in the generation of heat to trigger on-demand releases of two enzymes (ADA and GOx) via destroying the thermal-responsive nanoparticle shells. In the tumor microenvironment, GOx oxidizes glucose to form hydrogen peroxide (H2O2), which promotes the Fenton reaction of iron in SP@Hb, resulting in an enhanced ferroptosis effect and immunogenic cell death (ICD). In addition, ADA degrades high-level adenosine to reverse the immunosuppressive microenvironment, thus amplifying antitumor immune responses. Via NIR-II photoactivatable ferroptosis-immunotherapy, SPHGA shows an improved effect to absolutely remove bilateral tumors and effectively suppress tumor metastases in subcutaneous 4T1 breast cancer models. This study presents a dual-enzyme-based nanoagent with controllable therapeutic actions for effective and precise cancer therapy.


Subject(s)
Ferroptosis , Immunotherapy , Infrared Rays , Nanoparticles , Polymers , Semiconductors , Ferroptosis/drug effects , Animals , Immunotherapy/methods , Mice , Polymers/chemistry , Polymers/therapeutic use , Female , Nanoparticles/therapeutic use , Nanoparticles/chemistry , Cell Line, Tumor , Tumor Microenvironment/drug effects , Glucose Oxidase/metabolism , Glucose Oxidase/pharmacology , Humans , Mice, Inbred BALB C , Hemoglobins/pharmacology , Hemoglobins/metabolism
13.
Adv Sci (Weinh) ; 11(18): e2308251, 2024 May.
Article in English | MEDLINE | ID: mdl-38447152

ABSTRACT

Nanomedicine has reshaped the landscape of cancer treatment. However, its efficacy is still hampered by innate tumor defense systems that rely on adenosine triphosphate (ATP) for fuel, including damage repair, apoptosis resistance, and immune evasion. Inspired by the naturally enzymatic reaction of glucose oxidase (GOx) with glucose, here a novel "two birds with one stone" technique for amplifying enzyme-mediated tumor apoptosis and enzyme-promoted metabolic clearance is proposed and achieved using GOx-functionalized rhenium nanoclusters-doped polypyrrole (Re@ReP-G). Re@ReP-G reduces ATP production while increasing H2O2 concentrations in the tumor microenvironment through GOx-induced enzymatic oxidation, which in turn results in the downregulation of defense (HSP70 and HSP90) and anti-apoptotic Bcl-2 proteins, the upregulation of pro-apoptotic Bax, and the release of cytochrome c. These processes are further facilitated by laser-induced hyperthermia effect, ultimately leading to severe tumor apoptosis. As an enzymatic byproduct, H2O2 catalyzes the conversion of rhenium nanoclusters in Re@ReP-G nanostructures into rhenate from the outside in, which accelerates their metabolic clearance in vivo. This Re@ReP-G-based "two birds with one stone" therapeutic strategy provides an effective tool for amplifying tumor apoptosis and safe metabolic mechanisms.


Subject(s)
Apoptosis , Animals , Mice , Glucose Oxidase/metabolism , Neoplasms/metabolism , Humans , Disease Models, Animal , Cell Line, Tumor , Nanomedicine/methods , Tumor Microenvironment , Hydrogen Peroxide/metabolism , Polymers/chemistry , Polymers/metabolism
14.
Enzyme Microb Technol ; 177: 110428, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38547746

ABSTRACT

The sensing modified electrode was prepared using glucose oxidase immobilized onto vanadium pentoxide xerogel with glass/FTO as support electrode to evaluate the possibility to construct a V2O5/GOx Extended Gate Field Effect Transistor biosensor. Previously, our studies exhibited a sensitivity of V2O5 of 58.1 mV/pH. The use of Nafion® onto V2O5/GOx caused a decrease of mass loss after several cycles compared to the modified electrode without Nafion® during the EQCM and cyclic voltammetrics studies. Electrical characterization of V2O5/GOx demonstrated a tendency to stability after 200 s as a function of applied current. In presence of glucose and in different pH, the current decreased when the glucose concentration increased due to the lower active sites of enzyme. After ten voltammetric cycles, the total charge tends to structural stability. In pH = 5.0, the modified electrode based on V2O5/GOx Extended Gate Field Effect Transistor presented more tendency to sensitivity in different concentration of glucose.


Subject(s)
Biosensing Techniques , Electrodes , Enzymes, Immobilized , Glucose Oxidase , Glucose , Vanadium Compounds , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Enzymes, Immobilized/metabolism , Enzymes, Immobilized/chemistry , Glucose Oxidase/metabolism , Glucose Oxidase/chemistry , Glucose/analysis , Vanadium Compounds/chemistry , Transistors, Electronic , Hydrogen-Ion Concentration , Electrochemical Techniques/methods
15.
ACS Appl Bio Mater ; 7(3): 1862-1877, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38450575

ABSTRACT

Elevated levels of reactive oxygen species (ROS) have demonstrated efficacy in eliminating tumor cells by modifying the tumor microenvironment and inducing the polarization of tumor-associated macrophages (TAMs). Nevertheless, the transient nature and limited diffusion distance inherent in ROS present significant challenges in cancer treatment. In response to these limitations, we have developed a nanoparticle (MnClPc-HSA@GOx) that not only inhibits tumor energy metabolism but also facilitates the transition of TAMs from the M2 type (anti-inflammatory type) to the M1 type (proinflammatory type). MnClPc-HSA@GOx comprises a manganese phthalocyanine complex (MnClPc) enveloped in human serum albumin (HSA), with glucose oxidase (GOx) loaded onto MnClPc@HSA nanoparticles. GOx was employed to catalyze the decomposition of glucose to produce H2O2 and gluconic acid. Additionally, in the presence of MnClPc, it catalyzes the conversion of H2O2 into •O2- and 1O2. Results indicate that the nanoparticle effectively impedes the glucose supply to tumor cells and suppresses their energy metabolism. Simultaneously, the ROS-mediated polarization of TAMs induces a shift from M2 to M1 macrophages, resulting in a potent inhibitory effect on tumors. This dual-action strategy holds promising clinical inhibition applications in the treatment of cancer.


Subject(s)
Isoindoles , Nanoparticles , Neoplasms , Humans , Manganese/pharmacology , Glucose Oxidase/metabolism , Reactive Oxygen Species/metabolism , Hydrogen Peroxide/metabolism , Neoplasms/metabolism , Macrophages , Oxygen/metabolism , Energy Metabolism , Glucose , Tumor Microenvironment
16.
ACS Appl Bio Mater ; 7(5): 2781-2793, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38380497

ABSTRACT

A synergistic therapy agent (STA) with photothermal, photodynamic, chemodynamic, and starvation therapy (PTT, PDT, CDT, and ST) functions was developed. Hollow, mesoporous, and nearly uniform CeO2 nanoparticles (H-CeO2 NPs) were synthesized using a staged shape templating sol-gel protocol. Chlorin e6 (Ce6) was adsorbed onto H-CeO2 NPs, and a thin polydopamine (PDA) layer was formed on Ce6-adsorbed H-CeO2 NPs. Glucose oxidase (GOx) was bound onto PDA-coated Ce6-adsorbed H-CeO2 NPs to obtain the targeted STA (H-CeO2@Ce6@PDA@GOx NPs). A reversible photothermal conversion behavior with the temperature elevations up to 34 °C was observed by NIR laser irradiation at 808 nm. A cascade enzyme system based on immobilized GOx and intrinsic catalase-like activity of H-CeO2 NPs was rendered on STA for enhancing the effectiveness of PDT by elevation of ROS generation and alleviation of hypoxia in a tumor microenvironment. Glucose-mediated generation of highly toxic hydroxyl radicals (·OH) was evaluated for CDT. The effectiveness of PDT on glioblastoma T98G cells was markedly enhanced by O2 generation started by the decomposition of glucose. A similar increase in cell death was also observed when ST and CDT functions were enhanced by photothermal action. The viability of T98G cells decreased to 10.6% by in vitro synergistic action including ST, CDT, PDT, and PTT without using any antitumor agent.


Subject(s)
Cerium , Chlorophyllides , Indoles , Photochemotherapy , Photosensitizing Agents , Polymers , Porphyrins , Indoles/chemistry , Indoles/pharmacology , Cerium/chemistry , Cerium/pharmacology , Polymers/chemistry , Polymers/pharmacology , Humans , Porphyrins/chemistry , Porphyrins/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Cell Survival/drug effects , Glucose Oxidase/metabolism , Glucose Oxidase/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Materials Testing , Porosity , Particle Size , Drug Screening Assays, Antitumor , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemical synthesis , Cell Line, Tumor , Nanoparticles/chemistry
17.
Sensors (Basel) ; 24(4)2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38400442

ABSTRACT

Nanofiber technology is leading the revolution of wearable technology and provides a unique capability to fabricate smart textiles. With the novel fabrication technique of electrospinning, nanofibers can be fabricated and then manufactured into a durable conductive string for the application of smart textiles. This paper presents an electrospun nanofiber mesh-based (NF-Felt) string electrode with a conducting polymer coating for an electrochemical enzymatic glucose sensor. The surface area of a nanofiber matrix is a key physical property for enhanced glucose oxidase (GOx) enzyme binding for the development of an electrochemical biosensor. A morphological characterization of the NF-Felt string electrode was performed using scanning electron microscopy (SEM) and compared with a commercially available cotton-polyester (Cot-Pol) string coated with the same conducting polymer. The results from stress-strain testing demonstrated high stretchability of the NF-Felt string. Also, the electrochemical characterization results showed that the NF-Felt string electrode was able to detect a glucose concentration in the range between 0.0 mM and 30.0 mM with a sensitivity of 37.4 µA/mM·g and a detection limit of 3.31 mM. Overall, with better electrochemical performance and incredible flexibility, the NF-Felt-based string electrode is potentially more suitable for designing wearable biosensors for the detection of glucose in sweat.


Subject(s)
Biosensing Techniques , Nanofibers , Wearable Electronic Devices , Glucose/chemistry , Nanofibers/chemistry , Biosensing Techniques/methods , Polymers , Electrodes , Electrochemical Techniques/methods , Glucose Oxidase/metabolism
18.
Anal Chem ; 96(8): 3672-3678, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38361229

ABSTRACT

Redox potentiometry has emerged as a new platform for in vivo sensing, with improved neuronal compatibility and strong tolerance against sensitivity variation caused by protein fouling. Although enzymes show great possibilities in the fabrication of selective redox potentiometry, the fabrication of an enzyme electrode to output open-circuit voltage (EOC) with fast response remains challenging. Herein, we report a concept of novel enzymatic galvanic redox potentiometry (GRP) with improved time response coupling the merits of the high selectivity of enzyme electrodes with the excellent biocompatibility and reliability of GRP sensors. With a glucose biosensor as an illustration, we use flavin adenine dinucleotide-dependent glucose dehydrogenase as the recognition element and carbon black as the potential relay station to improve the response time. We find that the enzymatic GRP biosensor rapidly responds to glucose with a good linear relationship between EOC and the logarithm of glucose concentration within a range from 100 µM to 2.65 mM. The GRP biosensor shows high selectivity over O2 and coexisting neurochemicals, good reversibility, and sensitivity and can in vivo monitor glucose dynamics in rat brain. We believe that this study will pave a new platform for the in vivo potentiometric biosensing of chemical events with high reliability.


Subject(s)
Biosensing Techniques , Glucose Oxidase , Potentiometry , Reproducibility of Results , Glucose Oxidase/metabolism , Electrodes , Glucose , Oxidation-Reduction , Glucose 1-Dehydrogenase/metabolism
19.
Chempluschem ; 89(5): e202300601, 2024 May.
Article in English | MEDLINE | ID: mdl-38241333

ABSTRACT

An enzymatic fluorescent probe is developed for the selective detection of glucose. In this work, a Bovine Serum Albumin stabilized gold nanocluster (BSA-AuNCs) was synthesized by microwave assisted method, and it is modified with glucose oxidase, thereby a fluorescent enzymatic sensor (BSA-AuNCs@GoX) was designed for the sensitive detection of glucose with a limit of detection of 0.03 mM. The red fluorescence exhibited by the probe is quenched by the production of H2O2 on addition of glucose via. a static quenching mechanism from UV visible absorption and Fluorescence lifetime results. The developed probe exhibits good selectivity and sensitivity with other coexisting molecular species such as glycine, creatinine, methionine, histidine, uric acid, albumin, and ions such as sodium, potassium, calcium, magnesium, zinc etc. that appear in the body fluid. The practical applicability was studied in paper strip and extended its reproducibility in biological matrixes such as human serum and urine and found a good recovery percentage of 94-101 %. By this way, we have fabricated an effective fluorescent enzymatic "turn-off" sensing probe for the detection of glucose.


Subject(s)
Fluorescent Dyes , Glucose Oxidase , Glucose , Gold , Metal Nanoparticles , Serum Albumin, Bovine , Gold/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Serum Albumin, Bovine/chemistry , Metal Nanoparticles/chemistry , Animals , Humans , Cattle , Glucose/analysis , Glucose/chemistry , Fluorescent Dyes/chemistry , Biosensing Techniques/methods , Limit of Detection , Spectrometry, Fluorescence , Blood Glucose/analysis
20.
Environ Res ; 247: 118257, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38262511

ABSTRACT

This study introduces the UV/glucose-oxidase@Kaolin (GOD@Kaolin) coupled organic green rust (OGR) system (UV/OGR/GOD@Kaolin) to investigate the promotion of glucose oxidase activity by UV light and its synergistic degradation mechanism for photosensitive pollutants, specifically targeting the efficient degradation of 4-chlorophenol (4-CP). The enzyme system demonstrates its ability to overcome drawbacks associated with traditional Fenton systems, including a narrow pH range and high localized concentration of H2O2, by gradually releasing hydrogen peroxide in situ within a neutral environment. In the presence of UV radiation under specific conditions, enhanced enzyme activity is observed, resulting in increased efficiency in pollutant removal. The gradual release of hydrogen peroxide plays a crucial role in preventing unwanted reactions among active substances. These unique features facilitate the generation of highly reactive species, such as Fe(IV)O, •OH, and •O2-, tailored to efficiently target the organic components of interest. Additionally, the system establishes a positive iron cycle, ensuring a sustained reactive capability throughout the degradation process. The results highlight the UV/OGR/GOD@Kaolin system as an effective and environmentally friendly approach for the degradation of 4-CP, and the resilience of the enzyme extends the system's applicability to a broader range of scenarios.


Subject(s)
Environmental Pollutants , Water Pollutants, Chemical , Ultraviolet Rays , Hydrogen Peroxide/chemistry , Glucose Oxidase/metabolism , Kaolin , Glucose , Oxidation-Reduction , Water Pollutants, Chemical/chemistry
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