Small
·
2022
·Vol. 19
·期 5
·2206592
·
IF 15.153
Qiao Yu,Jie Zhou,Juan Song,Hong Zhou,Bin Kang,Hong-Yuan Chen,Jing-Juan Xu
Starvation therapy kills tumor cells via consuming glucose to cut off their energy supply. However, since glucose oxidase (GOx)-mediated glycolysis is oxygen-dependent, the cascade reaction based on GOx faces the challenge of a hypoxic tumor microenvironment. By decomposition of glycolysis production of H 2 O 2 into O 2 , starvation therapy can be enhanced, but chemodynamic therapy is limited. Here, a close-loop strategy for on demand H 2 O 2 and O 2 delivery, release, and recycling is proposed. The nanoreactor (metal-protein-polyphenol capsule) is designed by incorporating two native proteins, GOx and hemoglobin (Hb), in polyphenol networks with zeolitic imidazolate framework as sacrificial templates. Glycolysis occurs in the presence of GOx with O 2 consumption and the produced H 2 O 2 reacts with Hb to produce highly cytotoxic hydroxyl radicals (•OH) and methemoglobin (MHb) (Fenton reaction). Benefiting from the different oxygen carrying capacities of Hb and MHb, oxygen on Hb is rapidly released to supplement its consumption during glycolysis. Glycolysis and Fenton reactions are mutually reinforced by oxygen supply, consuming more glucose and producing more hydroxyl radicals and ultimately enhancing both starvation therapy and chemodynamic therapy. This cascade nanoreactor exhibits high efficiency for tumor suppression and provides an effective strategy for oxygen-mediated synergistic starvation therapy and chemodynamic therapy.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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化学生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2023
·Vol. 415
·期 10
·1877-1887
·
IF 4.3
Wang Yinghui,Yu Ling,Zhang Hui,Zhu Runzhi,Meng Zhe
An accurate and sensitive competitive enzyme-linked immunosorbent assay (ELISA) based on persistent luminescence nanoparticles Zn 2 GeO 4 :Mn 2+ , Eu 3+ (ZGME) was developed for detecting ochratoxin A (OTA), a powerfully toxic mycotoxin usually found in grains. As a signal output element of autofluorescence-free biosensors, ZGME can be integrated into ELISA with glucose oxidase (GOx)-binding OTA molecules due to its excellent pH-responsive persistent luminescence. In the absence of OTA, the OTA-GOx conjugate was captured by the anti-OTA monoclonal antibody (anti-OTA mAb) pre-coated on the 96-well plate. The results indicate a decrease in the pH value of the solution, which triggered the quenching of ZGME luminescence due to GOx-dependent gluconic acid production. The presence of OTA inhibited the binding of OTA-GOx on the plate, thus decreasing the production of gluconic acid and increasing the persistent luminous intensity of ZGME. Under the optimized concentrations of anti-OTA mAb and OTA-GOx, quantitative determination of OTA was achieved by plotting the increase or decrease in persistent luminescence intensity of ZGME at 535 nm. In this study, the linear range was from 0.1 μg L −1 to 63 μg L −1 , and the limit of detection (LOD) was as low as 0.045 μg L −1 . In five food samples (corn grit, brown rice, soybean, rice, and wheat), the results exhibited good stability and repeatability, with a recovery range from 81.3% to 94.4% and a relative standard deviation (RSD) of less than 4.2%. Hence, the established method provides a sensitive, accurate, and autofluorescence-free approach for the determination of OTA in different grain samples.
研究领域:
分析化学
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毒理学
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食品科学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2023
·
IF 8.6
Xingyu Fan,Botao Chen,Hui Xu,Anqiang Pan,Shuquan Liang,Songwen Tan,Yongju He
Depleting intracellular glutathione (GSH) has emerged as a potent strategy to combat cancer. However, the existing GSH-depleting agents are too toxic or ineffective and standalone GSH depletion fails to yield a satisfactory curative effect. Herein, we present an intelligent nanoparticle that possesses GSH depletion, glucose consumption accompanied with H2O2 production, and NO generation properties for multimodal cancer therapy. The nanoparticle is constructed by synthesis of tetrasulfide bond-doped mesoporous silica nanoparticles followed by conjugating glucose oxidase (GOx) on the surface and loading l-arginine (l-Arg) into the mesopores. In this nanoparticle, the doped tetrasulfide bonds can quickly deplete GSH, which increases the cellular reactive oxygen species concentration to induce ferroptosis and meanwhile triggers particle biodegradation to expose the loaded l-Arg. Moreover, the elevated H2O2 level activates l-Arg to release NO for NO therapy. GOx consumes glucose to initiate starvation therapy and simultaneously produces a large amount of H2O2. Importantly, the produced H2O2 can not only potentiate ferroptosis but also promote NO release to enhance NO therapy. Besides, NO could in turn improve the efficacy of starvation therapy by damaging the mitochondria to block energy supply. In vitro and in vivo studies demonstrate that the nanoparticles show a great synergistic effect of ferroptosis/starvation/NO therapy, which can significantly kill cancer cells and remarkably inhibit tumor growth without obvious side effects. Therefore, we think that the designed nanoparticles may provide a promising paradigm for synergistic cancer therapy and hold a prospect in clinical trials.
研究领域:
纳米技术
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癌症生物学
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药学
·
治疗学
✓ 已验证
DOI
高影响因子
ANALYTICAL SCIENCES
·
2024
·
IF 1.8
Bai Chen-Chen,Lang Jin-ye,Wang Xin-yu,Zhao Jia-meng,Dong Lin-Yi,Liu Jun-Jie,Wang Xian-Hua
Abstract The present article introduced an natural enzyme-covered/amino-modified Pd–Pt bimetallic-doped zeolitic imidazolate framework (NAPPZ) for ultrasensitive and specific detection of glucose. The dodecahedral nanomaterial zeolitic imidazolate framework (ZIF-8)-loaded Pd–Pt bimetallic nanoparticles endowed the composite with peroxidase-like activity. The modification with glucose oxidase (GOx) facilitated the rapid access of H 2 O 2 produced through glucose oxidation to the Pd–Pt nanoparticles vicinity reducing diffusion. GOx specifically catalyzes the transformation of glucose into H 2 O 2 , which then H 2 O 2 rapidly migrates to the Pd–Pt nanoparticles, catalyzing the oxidation of colorless o-phenylenediamine into the orange–yellow product 2,3-diaminophenazine. Based on the aforementioned cascade reaction, the NAPPZ and NAPPZ based on ChOx were utilized for detecting glucose in human urine samples and cholesterol in milk, respectively. The NAPPZ strategy presented a broad detection range (20–1100 μmol L −1 ) and a low detection limit (15.9 μmol L −1 ) for glucose, and the NAPPZ based on ChOx strategy approach offered a broad detection range (10–500 μmol L −1 ) and low detection limit (6.4 μmol L −1 ) for cholesterol. Therefore, this novel method holds significant potential in the areas of clinical diagnostics and food safety. Graphical abstract
研究领域:
材料科学
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分析化学
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生物技术
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临床诊断
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食品安全
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Qianqian Qiao,Zerui Liu,Fei Hu,Ziqiang Xu,Ying Kuang,Cao Li
Catalytic medicine, using enzymes or nanozymes, is an emerging method for cancer treatment. However, its applicability is limited by the low catalytic activity in the tumor microenvironment (TME). In this work, a versatile and synthesis-friendly nanozyme, CeO 2 Mn 1.08 O x nanoclusters, is prepared. This novel Ce─Mn heterojunction is formed by oxidation of CeO 2 nanoparticles through H 2 SO 4 /KMnO 4 . CeO 2 Mn 1.08 O x exhibits high multi-enzymatic catalytic activities and acts as a catalase (CAT), peroxidase (POD), and oxidase (OXD) mimics under acidic conditions. It can regulate the TME by relieving hypoxia and consuming endogenous glutathione (GSH). Glucose oxidase (GOx) is then incorporated into CeO 2 Mn 1.08 O x and linked with poly(ethylene glycol) (PEG) to obtain the cascade enzyme system (Ce─Mn)-PEI/GOx-PEG. CeO 2 Mn 1.08 O x exhibits CAT-like properties, which sensitize GOx-based starvation therapy, and POD- and OXD-like properties, which generate highly cytotoxic reactive oxygen species (ROS) in cancer cells. The glucose catabolic product, H 2 O 2 , is also used to generate O 2 and ROS. In addition, the heterojunction structure provides CeO 2 Mn 1.08 O x with near-infrared (NIR) photothermal capability, making it suitable for photothermal therapy (PTT). Density functional theory (DFT) calculations provide possible reasons for the high catalytic activity and photothermal capability of CeO 2 Mn 1.08 O x . When combining mild PTT with catalytic therapy, the cascade enzyme system (Ce─Mn)-PEI/GOx-PEG can efficiently ablate tumors.
研究领域:
癌症研究
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纳米技术
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生物医学工程
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诊疗学
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材料科学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Xi Zhou,Shuai Zhang,Yan Liu,Jiashen Meng,Muxue Wang,Yaoji Sun,Linbo Xia,Zhaozhi He,Wenxin Hu,Lei Ren,Zhiwei Chen,Xingcai Zhang
Nanozymes with peroxidase-like activity have great application potential in combating pathogenic bacterial infections and are expected to become an alternative to antibiotics. However, the near-neutral pH and high glutathione (GSH) levels in the bacterial infection microenvironment severely limit their applications in antibacterial therapy. In this work, a metal–organic framework (MOF)-based cascade catalytic glutathione-depleting system named MnFe2O4@MIL/Au&GOx (MMAG) was constructed. The MMAG cascade-catalyzed glucose to provide H+ and produces a large amount of toxic reactive oxygen species. In addition, MMAG consumed GSH, which can result in bacterial death more easily. Systematic antibacterial experiments illustrated that MMAG has superior antibacterial effects on both Gram-positive bacteria and Gram-negative bacteria.
研究领域:
纳米技术
·
生物医学工程
·
材料科学
·
细菌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2023
·
IF 6.7
Hang Jia,Shiqi Fan,Rui Cai,Zhouli Wang,Yahong Yuan,Tianli Yue
The abuse of antibiotics seriously threatens the public health, which leads to the urgent need to develop novel antimicrobial strategies. Reactive oxygen species (ROS) have been considered as an alternative approach for bacterial inactivation. At present, magnetic materials, especially iron oxide (Fe 3 O 4 ) nanoparticles have gained widely application in biomedical field. Owing to the intrinsic peroxidase-like activity, Fe 3 O 4 can catalyze the decomposition of hydrogen peroxide (H 2 O 2 ) to generate hydroxyl radical (⋅OH) under acidic conditions. Recently, Fe 3 O 4 -based peroxidase mimics have been developed for wound infection therapy. However, the direct introduction of H 2 O 2 with relative high concentration may induce undesired effect to normal tissues, and the infection site with near neutral pH still limits the antibacterial efficiency. Herein, carboxyl modified Fe 3 O 4 immobilized silver nanoparticles (Ag NPs) and glucose oxidase (GOx) were synthesized as a self-activated cascade regent. GOx endowed the hybrids with catalytic activity, which could convert glucose into gluconic acid, which activated the peroxidase-like activity of Fe 3 O 4 by decreasing the pH value. Moreover, the self-supplied H 2 O 2 was subsequently catalyzed by Fe 3 O 4 to generate ⋅OH. By combining the excellent antimicrobial performance of Ag NPs, the enzyme assisted magnetic hybrids exhibited robust antibacterial activity, which exhibited a great potential in bacteria-infected wound therapy.
研究领域:
生物医学工程
·
纳米技术
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材料科学
·
抗菌研究
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yuxuan Zhang,Xingchen Li,Xiaojun Ren,Dongzhou Wang,Yuechen Zhao,Yuan Wang,Shunzi Jin,Quan Lin,Kun Zou,Tiejun Wang
Insufficient accumulation of reactive oxygen species (ROS) due to tumor hypoxia significantly contributes to increased radiation resistance and the failure of radiotherapy (RT). Therefore, developing methods to alleviate hypoxia and boost ROS levels represents a promising strategy for enhanced radiosensitivity. This study introduced a self-cascade catalytic Pt@Au nanozymes as a radiosensitizer, using glucose oxidase (GOx)-, catalase (CAT)-, and peroxidase (POD)-like activities to improve hypoxia and increase ROS accumulation, thereby affecting glucose metabolism and enhancing the effects of RT. Pt@Au nanozymes exhibit GOx-like activity, which not only depletes glucose to induce starvation therapy, but also generates hydrogen peroxide (H2O2) for cascade reactions. Moreover, Pt@Au nanozymes demonstrate CAT-like activity, catalyzing the conversion of H2O2 to O2. This conversion effectively alleviates hypoxia, stabilizes ROS, increases DNA damage, significantly enhancing RT efficacy and sustaining the effects of starvation therapy. As high-Z materials, Pt@Au nanozymes can deposit more X-ray energy. Furthermore, the POD-like activity catalyzes the conversion of H2O2 into highly reactive hydroxyl radicals (·OH), which increases ROS levels and enhances RT. Pt@Au nanozymes serve as X-ray computed tomography (CT) imaging agents, allowing for clear differentiation between tumor and normal tissue boundaries and enhancing the precision of RT. In summary, Pt@Au nanozymes serve as effective radiosensitizers by depleting glucose to induce starvation therapy, enhancing cascade reactions, and inhibiting tumor proliferation. Through their self-cascade reactions, these nanozymes dramatically increase oxygen levels within tumors, reduce hypoxia, and enhance ROS levels. This advancement addresses the radioresistance associated with hypoxic tumors, paving the way for innovative strategies in RT.
研究领域:
癌症治疗
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纳米技术
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放射肿瘤学
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生物医学工程
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化学生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jing Gong,Shunhua Wang,Jie Liu,Yaowen Zhang,Jiyao Li,Hao Yang,Kunneng Liang,Yi Deng
Periodontitis, a chronic inflammatory condition associated with bacterial infection, is the leading cause of tooth loss in adults. Pathogenic bacteria that persist in deep periodontal pockets with hyperglycemic levels following traditional manual debridement can contribute to a persistent local inflammatory microenvironment, posing a significant challenge and highlighting the critical need for improved therapeutic approaches. In addition, the anaerobic environment during these treatments is beneficial to the colonization of anaerobes and may amplify inflammatory responses. Herein, we designed a glucose oxidase (GOx)-coating MXene-SnS 2 bio-heterojunctions (MS@G bio-HJs) for multi-modal and effective treatment of anti-bacteria and anti-inflammatory. Upon the hyperglycemic nidus in periodontal pockets, GOx catalyzes the conversion of glucose into hydrogen peroxide (H 2 O 2 ). Subsequently, the breakdown of H 2 O 2 into hydroxyl radicals through Sn 2+ /Sn 4+ -involved Fenton-like reactions enables in situ liberation of oxygen (O 2 ), contributing to relieve local hypoxia. The proposed bio-HJs presents a satisfactory bactericidal capability with anti-bacterial rates of more than 99 % upon near-infrared irradiation, in virtue of multi-modal therapies including photodynamic, photothermal and chemodynamic treatments. Furthermore, in vivo assays utilizing infectious rat models demonstrated that the proposed bio-HJs exhibits high biocompatibility and capacity to alleviate hypoxia and reduce pathogenic virulence factors, potentially contributing to periodontal tissue regeneration. These findings suggest that the versatile bio-HJs could be a promising therapeutic candidate for treating infectious periodontal diseases.
研究领域:
牙科学
·
生物材料
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纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Qihang Ding,Gongcheng Ma,Yuxin Xie,Hongrong Shi,Qian Bai,Xuechuan Hong,Hui Zhou,Ling Mei,Jong Seung Kim,Shuai Zhang
Starvation therapy, utilizing glucose oxidase (GOx) to deplete glucose and disrupt tumor energy, has shown promise in cancer treatment. However, this approach alone is insufficient to block ATP generation in tumors. Here, we introduce a self-‘cycling, boosting and propelling’ strategy, overcoming the ‘Achilles' heel’ of traditional starvation therapy by regulating the energy supply with CO. The high concentration of H 2 O 2 in the tumor microenvironment reacts with MnO 2 to generate Mn 2+ and O 2 . Mn 2+ catalyzes a Fenton-like reaction to produce hydroxyl radicals ( OH) for chemodynamic therapy and T1-weighted magnetic resonance imaging (MRI), while O 2 further enhances GOx-mediated glucose consumption, producing more H 2 O 2 . This process not only recycles H 2 O 2 but accelerates CO release, disrupting ATP synthesis and inhibiting tumor energy supply. Additionally, the gas released enhances nanoplatform motility, improving tumor penetration and overcoming the limited permeability of conventional nanoparticles. In vitro and in vivo studies demonstrated superior antitumor and antimetastatic efficacy, coupled with excellent biocompatibility. This strategy offers a promising solution to traditional starvation therapy's challenges, with strong potential for clinical translation and transformative cancer treatment.
研究领域:
癌症治疗
·
纳米医学
·
生物化学
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生物医学工程
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肿瘤学
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医学影像
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Shanshan Li,Kunpeng Lin,Peng Hu,Shaochen Wang,Shuang Zhao,Ying Gan,Lei Liu,Shuling Yu,Jiahua Shi
Phototherapies, including photothermal therapy (PTT) and photodynamic therapy (PDT) have been potential noninvasive therapeutic modality with high efficiency, however, there still exist some intrinsic limitations that impede their clinical applications. Herein, taking the advantages of the synergistic effect and high reactivity of manganese dioxide (MnO 2 ) nanosheets and glucose oxidase (GOx), multifunctional [email protected] 2 -MB-GOx nanoamplifier was constructed for enhanced PTT, PDT, and starvation therapy. In tumor microenvironment (TME), MnO 2 nanosheets on the surface of mesoporous polydopamine (MPDA) could react with endogenous hydrogen peroxide (H 2 O 2 ) and generate oxygen (O 2 ) to relieve tumor hypoxia, thus enhancing the efficacy of PDT and GOx catalysis. Glucose consumption under the catalysis of GOx will enhance the acidity of TME and increase intracellular H 2 O 2 concentration, which in turn promotes the production of O 2 by MnO 2 nanosheets, thus forming efficient cascade reaction and maximizing the efficacy of the functional agents. Furthermore, the heat generated by MPDA under the irradiation of 808 nm laser can accelerate chemical reactions, thus further enhancing synergistic therapeutic efficacy. In vitro/vivo results emphasize that enhanced cancer cell death and tumor inhibition are gained by modulating unfavorable TME with the functional nanosystem, which highlights the promise of the synthesized [email protected] 2 -MB-GOx nanomaterial to overcome the limitations of phototherapy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
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材料科学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biotechnology Journal
·
2022
·Vol. 17
·期 9
·2200098
·
IF 5.726
Wen Zhang,Wenbo Ye,Yajun Wang,Yunfeng Yan
Immobilized enzymes have drawn extensive attention due to their enhanced stability, easy separation from reaction mixture, and prominent recyclability. Nevertheless, it is still an ongoing challenge to develop potent immobilization techniques which are capable of stable enzyme encapsulation, minimal loss of activity, and modulability for various enzymes and applications. These microfibers were able to efficiently encapsulate bovine serum albumin (BSA), glucose oxidase (GOx), and horseradish peroxidase (HRP). But the physically adsorbed enzymes readily diffused into the catalytic reaction system. The leakage of enzymes could be substantially inhibited by conjugating to poly(acrylic acid) (PAA) and incorporating into alginate-based microfibers, enabling stable immobilization, improved recyclability, and enhanced thermostability. In addition, GOx and HRP-loaded microfibers were fabricated under the optimized conditions for the visual detection of glucose using the cascade reaction of these enzymes, showing sensitive color change to glucose with concentration range of 0–2 m m . Due to the tunability and versatility, this microfluidic-based microfiber platform may provide a valuable approach to the enzyme immobilization for the cascade catalysis and diagnoses with multiple clinical markers. Graphical and Lay Summary Development of potent techniques for the immobilization of enzymes with stable encapsulation, minimal loss of activity, and good reusability is an ongoing challenge. In this study, authors developed co-flow microfluidic devices for the fabrication of alginate-based microfibers with tunable size and crosslinking degree for the stable immobilization of glucose oxidase and horseradish peroxidase. This microfluidic platform has great potential in the construction of customizable enzyme-loaded microfibers for the cascade catalysis and diagnoses with multiple clinical markers.
研究领域:
生物化学
·
生物技术
·
材料科学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）