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LIFE SCIENCES · 2023 · IF 6.1

Application of f-FeNC@GOx cascade enzyme nanomaterials in the healing of infected wounds

Qingbo Yang,Chuangqi Mo,Pengfei Cui,Shuwen Zhou,Lin Qiu,Pengju Jiang,Yang Xuan,Hai Huang,Cheng Wang,Jianhao Wang

Aims Bacterial infection is a significant factor contributing to the deterioration of wounds, and the misuse of antibiotics has exacerbated bacterial resistance. Therefore, there is an urgent need to develop a novel antibacterial strategy to replace conventional therapies. This study aims to construct a self-activated cascade reaction nanozyme, f-FeNC@GOx, which triggers a cascade reaction in the presence of glucose. This cascade reaction generates highly toxic hydroxyl radicals ( OH), thereby achieving the goal of eliminating bacteria and promoting wound healing. Material and methods In vitro antibacterial experiments, bacterial spread plate method, Live/Dead staining, and crystal violet staining were conducted to analyze the antibacterial ability and mechanism of f-FeNC@GOx. In vivo experiments, a mouse wound model was established, and H&E and Masson staining of wound tissues were performed to assess the antibacterial activity of the f-FeNC@GOx in vivo . Key findings The in vivo and in vitro experiments confirmed that f-FeNC@GOx exhibited significant antibacterial effect against both Staphylococcus aureus and Escherichia coli in the presence of glucose. Furthermore, it showed optimal wound healing performance in the wound models. Significance These findings suggested that f-FeNC@GOx was a novel and effective antibacterial nanomaterial, which provided a promising antibacterial strategy using nanoenzyme based cascade reaction.

CAS / MDL: 75-12-7
研究领域: 生物医学工程 · 纳米医学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nanoscale · 2021 ·Vol. 13 ·期 39 ·16571-16588 · IF 7.79

A multimodal strategy of Fe3O4@ZIF-8/GOx@MnO2 hybrid nanozyme via TME modulation for tumor therapy

Yu Zhang,Yifeng Yang,Jinsheng Shi,Lili Wang

Weak acidity (6.5–6.9) and limited H2O2 level in the tumor microenvironment (TME) usually impact the therapeutic effect of chemodynamic therapy (CDT) for cancer. A Specific TME promotes the formation of an immunosuppressive microenvironment and results in high rate of recurrence and metastasis of cancer. Fe3O4@ZIF-8/GOx@MnO2 multi-layer core shell nanostructure was constructed as a hybrid nanozyme. After magnetic targeting of the tumor site, the outermost MnO2 shell catalyzed H2O2 in TME to produce O2 and was broken due to the reaction with glutathione. Due to the acid response, the ZIF-8 layer would crack and release glucose oxidase (GOx) and Fe3O4. The generated O2 was utilized by GOx in starvation therapy to consume glucose and produce H2O2 and gluconic acid. The Fenton reaction efficiency of Fe(II) was improved by the increased H2O2 concentration and the enhanced acidity in TME. At the same time, the intrinsic photothermal effect of Fe3O4 upon 808 nm laser irradiation promoted the activity of MnO2 and GOx as oxidase, and Fe(II) as catalase-like, and ablated the primary tumor. Moreover, the hybrid nanozyme can facilitate the transformation of M2-type macrophages to M1-type, and strong systemic antitumor immune effect was induced. A synergy of multiple therapeutic modes including starvation therapy, CDT, photothermal therapy (PTT), and immunotherapy can be realized in the hybrid nanozyme for tumor therapy.

CAS / MDL: 9001-37-0 10196-18-6
研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学 · 免疫学
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NEW JOURNAL OF CHEMISTRY · 2022 ·Vol. 47 ·期 5 ·2248-2256 · IF 3.925

Co-immobilization of PPL and GOx on DUT-5/PVDF hybrid membranes and catalytic activity in the cascade oxidation of glucose and styrene

Defeng Hu,Rongzhong Li,Yide Han,Hao Meng,Xia Zhang

Currently, the co-immobilization of multi-enzymes on a solid carrier and their applications in cascade catalytic reactions are primarily studied. In this study, a MOF/polymer porous membrane composed of DUT-5 incorporated polyvinylidene fluoride (PVDF) is constructed and employed in the co-immobilization of porcine pancreatic lipase (PPL) and glucose oxidase (GOx) for the first time. The loading amounts of DUT-5 nanoparticles were varied to optimize the subsequent immobilization efficiency for the two enzymes. The adsorption conditions, isotherms and kinetics for both PPL and GOx were investigated systematically, and the optimum adsorption conditions were determined and used in the co-immobilization of the two enzymes step by step. It is interesting that the maximum adsorption amounts for the two enzymes in the co-immobilization process are similar to the results obtained in the single enzyme immobilization, which indicates the better compatibility of PPL and GOx in the hybrid membranes. The catalytic activities of the co-immobilized enzymes were evaluated using a cascade oxidation reaction, in which H2O2 produced in the GOx-catalyzed oxidation of glucose worked as the oxidant in the subsequent oxidation of styrene. Further, the catalytic efficiency of the co-immobilized enzymes is compared to that of the mixed free PPL and GOx. The improved catalytic rates and better reusability of the co-immobilized enzymes highlight the broader applications of MOF-based membranes in the co-immobilization of two or more enzymes and the catalytic applicabality in the cascade organic reactions.

CAS / MDL: 9001-37-0
研究领域: 生物化学 · 材料科学 · 酶工程
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International Journal of Nanomedicine · 2022 · IF 7.033

GOx-Functionalized Platelet Membranes-Camouflaging Nanoreactors for Enhanced Multimodal Tumor Treatment

Ying Du,Shujun Wang,Jianfeng Luan,Meilin Zhang,Baoan Chen,Yanfei Shen

Background Glucose oxidase (GOx)-based starvation therapy is a new cancer treatment strategy. However, the characteristics such as limited curative effect and hypoxic tumor environment hinder its further application seriously.Methods Herein, doxorubicin (DOX) loaded in hollow mesoporous copper sulfide (HMCuS) nanoparticles assembled with manganese dioxide (HMMD) as nanoshell was prepared. We developed a targeted enhanced cancer treatment method to camouflage HMMD by GOx-functionalized platelet (PLT) membranes (HMMD@PG).Results GOx can be specially transported to the tumor site with PLT membrane for effective starvation treatment. Glucose and oxygen (O2) in the tumor were converted to H2O2 under the catalysis of GOx. HMMD can catalyze H2O2 to produce O2 and consume glutathione (GSH) in time, which regulates the tumor microenvironment (TME) and improves the adverse conditions of anti-tumor. In addition, DOX encapsulated in HMCuS-MnO2 release was accelerated from the nanoparticles after the “gatekeeper” MnO2 is consumed. The study of anti-tumor mechanism shows that the remarkable tumor suppressive ability of HMMD@PG comes from the three peaks synergy of starvation treatment, photothermal treatment (PTT), and chemotherapy. This nanoplatform disguised by PLT membrane has significant tumor inhibition ability, good biocompatibility and almost has no side effects in main organs.Conclusion This work broadens the application mode of GOx and shows the new development of a multi-mode collaborative processing system of nanoplatforms based on cell membrane camouflage.

研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMISTRY-A EUROPEAN JOURNAL · 2021 ·Vol. 28 ·期 1 ·e202102885 · IF 5.236

“Four-in-One” Nanozyme and Natural Enzyme Symbiotic System of Cu2-xSe−GOx for Cervical Cancer Therapy

Yubo Hu,Ke Wang,Cong Ye

Graphical The nanozyme@natural enzyme symbiotic system of Cu 2- x Se−GOx exhibited prominent “four-in-one” cascaded catalytic enzyme activities including catalase, peroxidase, glutathione oxidase and glucose oxidase. The ingenious Cu 2- x Se−GOx could significantly induce the accumulation of reactive oxygen species (ROS) at tumor regions; this results in a tumor microenvironment (TME)-activated “four-in-one” enzyme cascade that is lethal to cervical cancer. All in all, Cu 2- x Se−GOx can act as a high-performance and safe bioactive material for cancer treatment. Cervical cancer, as a common malignant tumor of the reproductive system, seriously threatens women‘s life and health, and is difficult to be cured by traditional treatments, such as surgery, chemotherapy and radiotherapy. Fortunately, tumor microenvironment (TME)-activated catalytic therapy with high efficiency and reduced off-target toxicity has emerged as a novel treatment model. Herein, we designed a “four-in-one” nanozyme and natural enzyme symbiotic system of Cu 2- x Se−GOx for TME-triggered cascaded catalytic enhanced cancer treatment. In response to unique TME, Cu 2- x Se with catalase activity could effectively catalyze over-expressed H 2 O 2 in cancer cells into O 2 . Subsequently, the glucose oxidase (GOx) could deplete intracellular glucose with the assistance of O 2 ; this not only achieves starvation therapy, but also regenerates H 2 O 2 to boost the generation of highly cytotoxic . OH due to the peroxidase activity of Cu 2- x Se. Moreover, although the free-radical scavenger glutathione (GSH) is overexpressed in tumor cells, Cu 2- x Se with glutathione oxidase activity could effectively consume GSH for enhanced ROS production. Thus, the “four-in-one” nanozyme@natural enzyme symbiotic system of Cu 2- x Se−GOx could induce significant ROS accumulation at the tumor regions, thus providing a potential approach for the treatment of cervical cancer.

研究领域: 癌症生物学 · 纳米技术 · 生物医学工程 · 药学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2025 · IF 9.7

Glucose-responsive multifunctional hydrogel incorporating GOx@ZIF-8 for NO/Zn2+-mediated antibacterial and pro-angiogenic diabetic wound healing

Jialiang Pan,Chenhong Liu,Zhiqiang Wang,Wenbo Shi,Tianhao Zhao,Qingcong Wei,Qing Zhang,Zhengyu Bai

The hyperglycemic microenvironment of diabetic chronic wounds is a major driver of severe bacterial infections, excessive inflammatory responses, and impaired angiogenesis, all of which delay wound healing. To address these challenges, we prepared a glucose oxidase (GOx)–loaded zeolitic imidazolate framework-8 (GOx@ZIF-8). Furthermore, a multifunctional hydrogel (AACZ) was fabricated by incorporating 5-methylfurfural– and L-arginine–grafted alginate and maleimide–grafted chondroitin sulfate with GOx@ZIF-8 through the Diels–Alder reaction. Results showed that immobilized GOx remained active for a longer time than of free GOx. At the wound site, GOx catalyzed the conversion of excess glucose to gluconic acid and hydrogen peroxide (H 2 O 2 ). The reduced pH in the local region induced Zn 2+ release from zeolitic imidazolate framework-8, simultaneously, H 2 O 2 mediated the generation of nitric oxide (NO) from L-arginine. The synergy between Zn 2+ and NO endowed AACZ with excellent antibacterial properties. The biocompatible hydrogel promoted cell proliferation and migration, regulated local blood glucose levels, inhibited bacterial activity, alleviated inflammation and promoted angiogenesis and collagen deposition at the diabetic wound site. These findings suggest that AACZ holds promise as a responsive dressing material in healing for complex wounds.

研究领域: 生物材料 · 纳米医学 · 伤口愈合 · 生物化学 · 糖尿病研究
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Nano Research · 2020 ·Vol. 14 ·期 1 ·222-231 · IF 8.183

ATP-responsive hollow nanocapsules for DOX/GOx delivery to enable tumor inhibition with suppressed P-glycoprotein

Zhu Huimin,Cao Guodong,Fu Yike,Fang Chao,Chu Qiang,Li Xiang,Wu Yulian,Han Gaorong

Multidrug resistance (MDR) restricts chemotherapy efficacy due to P-glycoprotein (P-gp) mediated drug efflux, whereas current approaches to suppressing P-gp expression suffer from intrinsic challenges, such as low transfection, high toxicity and poor specificity. Here, hollow ferric-tannic acid complex nanocapsules (HFe-TA), which can be effectively degraded by the reaction with adenosine triphosphate (ATP), are synthesized for the delivery of glucose oxidase (GOx) and doxorubicin (DOX) for tumor treatment. The findings indicate that the intracellular ATP is significantly decreased due to the combined effect of HFe-TA degradation and GOx-mediated glucose consumption. Along with this ATP down-regulation, P-gp expression of tumor cells is suppressed remarkably, which in turn promotes the intracellular accumulation and anticancer efficacy of DOX. In addition, the production of OH by Fe ions released from HFe-TA is promoted by the by-products of the oxidation of glucose process by GOx. In consequence, HFe-TA nanocapsules loaded with DOX and GOx enable significant inhibition effect to tumors both in vitro and in vivo due to the synergistic effect of cascade reactions. This study has therefore provided an alternative therapeutic platform for effective tumor inhibition with the potential in overcoming intrinsic MDR.

研究领域: 纳米技术 · 药学 · 癌症研究 · 生物医学工程
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MICROCHIMICA ACTA · 2021 ·Vol. 188 ·期 2 ·1-9 · IF 5.833

Ultrasensitive electrochemical immunosensor based on the signal amplification strategy of the competitive reaction of Zn2+ and ATP ions to construct a “signal on” mode GOx-HRP enzyme cascade reaction

Li Wenjun,Chen Siyu,Yang Yue,Song Yiju,Ma Chaoyun,Qiao Xiuwen,Hong Chenglin

A GOx/HRP@ZIF-90 nanomaterial is proposed by coating GOx and HRP in ZIF-90 using a bio-simulated mineralization method to improve the tolerance of the enzyme to the external environment. In the detection process, the ZIF-90 is turned on under mild conditions by the competitive reaction of ATP with Zn 2+ and imidazole-2-carboxaldehyde (2-ICA), and the electrical signal of the system is amplified by the enzyme cascade reaction of GOx and HRP. Finally, based on the signal amplification strategy of the competitive reaction between Zn 2+ and ATP to construct a “signal on” mode, electrochemical immunosensor of GOx-HRP enzyme–linked cascade reaction was prepared. The proposed electrochemical immunosensor shows an excellent analytical performance when detecting CA-125, with good selectivity and stability, with a detection range of 0.1 pg mL −1 –40 ng mL −1 and a detection limit of 0.05 pg mL −1 . The test has been performed using chronoamperometry under a constant voltage of −0.4 V. The immunosensor also shows an excellent performance when analysing human blood samples. The recovery of the immunosensor is 97.94–101.8%, with a relative standard deviation of 3.7–6.1%. The proposed sensor provides a novel idea for clinical use of GOx and HRP enzymes and a new method for the clinical detection of tumor markers. Graphical abstract

研究领域: 生物医学工程 · 分析化学 · 肿瘤标志物检测
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHEMICAL JOURNAL · 2024 · IF 4.9

Construction of Pt-GOx@H-ZIF-8 core–shell structure for the detection of glutathione

Xinyuan Yan,Juan Chai,Luohao Yuan,Hongfeng Yin

Glutathione (GSH), as an significant intracellular antioxidant, plays a vital role in preserving the balance of cellular redox homeostasis. The accurate and sensitive detection of GSH is essential for understanding the cellular redox status and for the diagnosis and treatment of many diseases. Herein, a core–shell structure composed of glucose oxidase (GOx), platinum (Pt) nanoparticles and a zeolitic imidazolate framework (ZIF-8) shell was constructed. Pt NPs in the core–shell showed high peroxidase-like catalytic activity. The as-prepared Pt-GOx@H-ZIF-8 can be utilized for colorimetric detection of GSH, exhibiting a broad linear range from 0.5 to 90 μM, and a low limit of detection (LOD) of 0.4 μM. Pt-GOx@H-ZIF-8 showed excellent sensitivity, selectivity and stability towards glutathione detection, making it a promising candidate for intracellular antioxidants.

研究领域: 分析化学 · 生物传感器 · 纳米材料 · 生物医学工程
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ANALYTICA CHIMICA ACTA · 2023 · IF 6.2

Noninvasive glucose monitoring using portable GOx-Based biosensing system

Yingying Xiao,Lanlan Hou,Mengzhu Wang,Ruping Liu,Lu Han,Mukhurov Nikolai,Siqi Zhang,Chuantong Cheng,Kuan Hu

Wearable biosensors have gained huge interest due to their potential for real-time physiological information. The development of a non-invasive blood glucose device is of great interests for health monitoring in reducing the diabetes incidence. Here, we report a sandwich-structured biosensor that is designed for glucose levels detection by using sweat as the means of monitoring. The Prussian blue nanoparticles (PBNPs) and carboxylated carbon nanotubes (MWCNT-COOH) were self-assembled on the electrode to improve the electrochemical performance and as the sensor unit, glucose oxidase (GOx) was immobilized by chitosan (CS) as the reaction catalysis unit, and finally encapsulated with Nafion to ensure a stable performance. As a result, the GOx/PBNPs/MWCNT-COOH sensor displays a low detection limit (7.0 μM), high sensitivity (11.87 μA mM −1  cm −2 ), and excellent interference resistance for a full sweat glucose application range (0.0–1.0 mM) for both healthy individuals and diabetic patients. Additionally, the glucose sensor exhibits stable stability for two weeks and can be successfully applied to screen-printed carbon electrodes (SPCE), demonstrating its great potential for personalized medical detection and chronic disease management.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL RESEARCH · 2022 · IF 8.431

Green rust (GR) and glucose oxidase (GOX) based Fenton-like reaction: Capacity of sustainable release, promoted conversion of glucose through GOX-iron and pH self-adjustment

Zefeng Li,Meng Li,Bin Tan,Ning Du,Qian Zhang,Chengwei Li,Yibo Zhang,Jiawei Li,Jiayi Li

The Fenton reaction is regarded as highly efficient for the degradation of organic contaminants . However, the traditional Fenton reaction is still flawed in a narrow pH working range and low utilization efficiency of the reagents. Based on two striking features, a sustained release of H 2 O 2 in-situ under the catalysis of glucose oxidase (GOX) and the rapid electron donation & transferability from green rust (GR), an adaptable biological Fenton-like system (GGGMFs) was established. The coupling roles of glucose, GOX and GR in the degradation of 3,4-dimethylaniline (3,4-DMA) and the types of reactive species were deduced by electron spin resonance (ESR), etc.. Results demonstrated that the suitable pH range of the system was optimized from acidic to circumneutral, which was favorable for practical application, owing to the heterogeneous formation of GR and the pH self-adjustable capacity of GOX-Glucose. Meanwhile, hydroxyl radical (·OH), superoxide radical (·O 2 − ) and Fe (IV) were identified to be the main oxidizing reactive species. Taking different selectivity of the reactive species to certain pollutant functional groups into consideration, the degradation pathways of 3,4-DMA were proposed. Moreover, it was shown that GR not only acted as the activating substance of the Fenton-like reaction, but also enhanced the activity of GOX, resulting in the promotion of glucose conversion in GGGMFs. This study shed light on the enhancement mechanism consisting of two aspects: (i) the elimination of product inhibition (ii) the formation of a 2Fe(III)-FAD complex with FAD , the active center of GOX, which prompted the electronic transfer in the enzyme catalytic reaction.

研究领域: 环境科学 · 化学工程 · 生物技术
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2018 · IF 8.097

Bioinspired Dual-Enzyme Colloidosome Reactors for High-Performance Biphasic Catalysis

Zhenning Liu,Bingdi Wang,Shenghui Jin,Zhida Wang,Lei Wang,Song Liang

In this paper, a novel method for the construction of colloidosomes as a microreactor for dual-enzyme cascade biphasic reaction has been reported. A lipase–glucose oxidase (GOx) enzyme pair is employed in this system. A water-soluble enzyme GOx is compartmentalized inside the colloidosomes. A hydrophobic environment-favored enzyme Candida Antarctica lipase B (CalB) is adsorbed on the outer surfaces of the colloidosomes. The catalysis system is set up by introducing these dual-enzyme-immobilized microcapsules into acetic ether. H2O2 is produced in the aqueous phase by the doped GOx, and then H2O2 diffused out of the microcapsules is utilized by CalB to catalyze the oxidation of ethyl acetate. Finally, the formed peracids oxidized N-heteroaromatic in situ. Furthermore, no obvious yield decline is observed in four reaction cycles. Thus, our work provides a new strategy for the design of high-performance biomimicking reactors for multiple enzyme cascade reactions and further expands the potential application area of colloidosomes.

研究领域: 生物化学 · 材料科学
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