BIOSENSORS & BIOELECTRONICS
·
2016
·
IF 7.476
Qinghua Hu,Changmin Yu,Xitao Xia,Fang Zeng,Shuizhu Wu
Biothiols like Cys, Hcy and GSH play important roles in various physiological and pathological processes, and it is still challenging to simultaneously and discriminatively detect GSH and Cys/Hcy due to their similar structures and reaction activities. Hence, it would be highly desirable to design a fluorescent probe for simultaneously discriminating GSH and Cys/Hcy in biological samples with no spectral crosstalk , few interferences and rapid response. Herein, through coupling two fluorophores with biothiol-sensitive linker, we developed a fluorescent probe , which has two biothiol-responsive and distinctly-separated emissions via independent visible-light excitations, for simultaneously discriminating GSH and Cys/Hcy with near-infrared and green emissions. The probe is operable in human serum samples, thus holding promise for diagnostic-related applications. Moreover, the probe shows quite good properties. First, it exhibits a rapid response (within a few minutes) with highly selective and sensitive detection for GSH and Cys/Hcy. Second, it offers an apparent colorimetric and two fluorescence emission signals without spectral crosstalk . Third, it shows low cytotoxicity. Therefore, it would provide a useful method for further elucidating the roles of biothiols as well as for conducting pathological analysis for diseases involving biothiols.
研究领域:
生物化学
·
分析化学
·
医学诊断
✓ 已验证
DOI
高影响因子
ACS Nano
·
2025
·
IF 16
Mengsi Zhang,Hao Zheng,Xuanqi Zhu,Shuwei Liu,Hao Jin,Yang Chen,Lanlan Wan,Songling Zhang,Hao Zhang
Disulfidptosis and ferroptosis are recently identified programmed cell deaths for tumor therapy, both of which highly depend on the intracellular cystine/cysteine transformation on the cystine transporter solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 (SLC7A11/GSH/GPX4) antioxidant axis. However, disulfidptosis and ferroptosis are usually asynchronous due to the opposite effect of cystine transport on them. Herein, systematic glucose deprivation, by both inhibiting upstream glucose uptake and promoting downstream glucose consumption, is proposed to synchronously evoke disulfidptosis and ferroptosis. As an example, Au nanodots and Fe-apigenin (Ap) complexes coloaded FeOOH nanoshuttles (FeOOH@Fe-Ap@Au NSs) are employed to regulate the SLC7A11/GSH/GPX4 axis for performing disulfidptosis- and ferroptosis-mediated tumor therapy synchronously. In this scenario, Au nanodots exhibit glucose oxidase-like activity when consuming massive glucose. Meanwhile, Ap can inhibit glucose uptake by downregulating glucose transporter 1, depriving glucose fundamentally. The systematical glucose deprivation limits the supplement of NADPH and suppresses cystine/cysteine transformation on the SLC7A11/GSH/GPX4 axis, thus solving the contradiction of cystine transport on disulfidptosis and ferroptosis. In addition, the efficient delivery of exogenous iron ions by FeOOH@Fe-Ap@Au NSs and self-supplied H2O2 through Au nanodots-catalytic glucose oxidation facilitate intracellular Fenton reaction and therewith help to amplify ferroptosis. As a result of synchronous occurrence of disulfidptosis and ferroptosis, FeOOH@Fe-Ap@Au NSs exhibit good efficacy in an ovarian cancer therapeutic model.
研究领域:
肿瘤治疗
·
分子生物学
·
纳米医学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Sihan Shen,Ran Xie,Yiqun Wang,Lingyu Jia,Zhangran Zhu,Hai Ma,Lifang Wang,Feng Sui,Yu Zhao,Qinghe Zhao,Yanjun Chen
Ferroptosis represents a novel procedure of programmed cell death driven by iron-dependent lipid peroxidation, and may offer a promising strategy for cancer therapy. In this study, we developed poly (2-ethyl-2-oxazoline)-poly (lactic acid)-SS-poly (β-amino ester) (PEOz-PLA-SS-PBAE) loaded with β-elemene. The disulfide bond mediated depletion of glutathione (GSH) and inactivation of glutathione peroxidase 4 (GPX4) will lead to inactivation of the antioxidant system of the tumor cell, and β-elemene has the capacity to generate reactive oxygen species (ROS), and the above changes would induce a disruption of the redox balance within the tumor cell, resulting in ferroptosis of the tumor cell. In conclusion, in this study, water insoluble β-elemene was solubilized by the triblock copolymer to construct a pH/GSH dual-responsive nano-delivery system, and combined with iron death and chemotherapy to exert combinatory inhibition effect on breast cancer cells, which provides a new idea for the potential clinical application of β-elemene
研究领域:
肿瘤学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2015
·
IF 6.409
Yanxue Xu,Lei Zhang,Yuan Liu,Zhaoyu Jin,Qian Zhao,Feng Yang,Dan Xiao
Electrochemiluminescence (ECL) material Ru-dpq (Ru(bpy) 2 dpq 2+ , dpq=1,10-phenanthroline-5,6-dione; bpy=2,2′-bipyridine) is found to be produced strong and stable anodic ECL signal, which could be quenched by reduced glutathione (GSH) and exhibits high sensitivity and selectivity simultaneously. According to the mass spectra of Ru-SG (product of Ru-dpq reacted with GSH), and single crystal structure of the final oxidized product Ru-dcbpy ((Ru(bpy) 2 dcbpy 2+ , dcbpy=3,3-dicarboxy-2,2-bipyridine), we propose a new interacted mechanism between Ru-dpq and GSH. A good linear relation is estimated to be from 0.1 pM to 50 μM in the presence of calcium ion and the detection limit is as low as 0.087 pM (with the signal-to-noise ratio of 3). The relative standard deviation is 2.3% (for three repeated measurements). Furthermore, the ECL signal of Ru-dpq under a constant potential (1.2 V) is extremely stable and the intensity could be maintained over 600 s, which promotes us to determine the concentration of GSH via chronoamperometry .
研究领域:
分析化学
·
电化学
·
生物分析
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOTECHNOLOGY
·
2024
·
IF 4.1
Gang Luo,Wen Yang,Zijian Geng,Yiyi Cheng,Yingqing Xu,Yimeng Xiao,Jiying Liu
The Pichia pastoris expression system is a favorable platform for production of pharmaceutical proteins. Treatment of strains with N-acetyl-L-cysteine (NAC) has been shown to enhance the yield of recombinant proteins, thereby contributing to a reduction in production costs. However, the specific mechanism of action of NAC remains unclear. Previous research has indicated that glutathione (GSH) and autophagy are involved in the increased production of human serum albumin and porcine follicle-stimulating hormone β (HSA-pFSHβ) by NAC. This study investigated the potential interaction between GSH and autophagy in the production of HSA-pFSHβ. The findings indicated that sulfhydryl-free antioxidants such as melatonin, vitamin C, or vitamin E did not exhibit similar effects to NAC in enhancing HSA-pFSHβ yield. Moreover, NAC was found to enhance HSA-pFSHβ production by modulating GSH metabolism to reduce GSH consumption, increase total GSH levels, as well as glutathione peroxidase (GSH-Px) and glutathione reductase (GR) activities. Additionally, inhibition of autophagy through disruption of autophagy scaffolding proteins Atg1 or Atg11 led to an increase in recombinant HSA-pFSHβ production. Furthermore, NAC significantly decreased the phosphorylation of Slt2, and the absence of the SLT2 gene influenced the effect of NAC on HSA-pFSHβ secretion by modulating mitophagy and GSH metabolism. In conclusion, these results suggest a complex interplay between GSH metabolism and autophagy in the regulation of NAC-induced HSA-pFSHβ secretion.
研究领域:
分子生物学
·
生物技术
·
药用蛋白质
·
酵母表达系统
✓ 已验证
DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
·
IF 4.6
Xiang-Cheng Lin,Jian Liu,Miaomiao Hu,Lingjun Song,Minzhe Li,Qinjie Kou,Rong Huang,Lixian Sun,Changchun Wen
The abnormal fluctuations of glutathione (GSH) in vivo often reflect disease progression and are closely linked to human metabolism and physiological functions. Highly sensitive and selective detection of GSH is crucial for guiding early diagnosis and treatment; however, achieving this remains a significant challenge. In this study, we developed an enzyme activity sensor platform for the efficient detection of GSH. This platform utilizes Au@CuS core–shell materials loaded with CuO 2 nanoparticles to create a composite nanosensor system. Under slightly acidic conditions, CuO 2 on the nanomaterial’s surface decomposes into H 2 O 2 and Cu 2+ ions. The generated H 2 O 2 then reacts with tetramethylbenzidine (TMB) in the presence of peroxidase-like CuS to yield oxidized tetramethylbiphenyl ( OX TMB), which generates a distinctive Raman signal. Upon addition of GSH to the system, the unique OX TMB signal diminishes due to GSH’s strong antioxidant capacity and the consequent consumption of OX TMB. This sensing method enables sensitive detection of GSH, with a detection limit as low as 1.2 × 10 -13 mol∙L -1 . This approach holds promise for providing researchers with rapid and precise in vitro analysis of GSH, serving as an indicator for early disease diagnosis and real-time evaluation of treatment efficacy.
研究领域:
生物化学
·
纳米医学
·
诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 19
·4274-4286
·
IF 7
Jingge Zhang,Enna Ha,Danyang Li,Shuqing He,Luyang Wang,Shaolong Kuang,Junqing Hu
Nanozymes mediated catalytic therapy can produce toxic reactive oxygen species (ROS) and destroy the metabolic balance of tumor cells, providing a new direction for cancer treatment. However, the catalytic efficiency of a single nanozyme is limited by the complexity of the tumor microenvironment (hypoxia, GSH overexpression, etc.). In order to overcome these problems, we designed flower-like Co-doped FeSe2 (Co–FeSe2) nanozymes by a simple wet chemistry method. Co–FeSe2 nanozymes not only exhibit high POD and OXD-mimicking activities for facile kinetics, but also effectively consume over-expressed glutathione (GSH), inhibiting the consumption of generated ROS and destroying the metabolic balance of the tumor microenvironment. These catalytic reactions trigger cell death through apoptosis and ferroptosis dual pathways. More importantly, under the NIR II laser irradiation, the catalytic activities of Co–FeSe2 nanozymes are boosted, confirming the photothermal and catalytic synergistic tumor therapy. This study takes advantage of self-cascading engineering that offers new ideas for designing efficient redox nanozymes and promoting their clinical translation.
研究领域:
癌症治疗
·
材料科学
·
纳米医学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Discover Nano
·
2023
·Vol. 18
·期 1
·1-14
·
IF 0
Shao Runrun,Qiao Xiaofang,Cao Linlin,Man Jianliang,Guo Lingyun,Li Lanlan,Liu Wen,Li Lihong,Wang Bin,Guo Lixia,Ma Sufang,Zhang Boye,Wang Haojiang,Yan Lili
The development of nanoparticles capable of inducing reactive oxygen species (ROS) formation has become an important strategy for cancer therapy. Simultaneously, the preparation of multifunctional nanoparticles that respond to the tumor microenvironment is crucial for the diagnosis and treatment of tumors. In this study, we designed a Molybdenum disulfide (MoS 2 ) core coated with Manganese dioxide (MnO 2 ), which possessed a good photothermal effect and could produce Fenton-like Mn 2+ in response to highly expressed glutathione (GSH) in the tumor microenvironment, thereby generating a chemodynamic therapy (CDT). The nanoparticles were further modified with Methoxypoly(Ethylene Glycol) 2000 (mPEG-NH 2 ) to improve their biocompatibility, resulting in the formation of MoS 2 @MnO 2 -PEG. These nanoparticles were shown to possess significant Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) imaging capabilities, making them useful in tumor diagnosis. In vitro and in vivo experiments demonstrated the antitumor ability of MoS 2 @MnO 2 -PEG, with a significant killing effect on tumor cells under combined treatment. These nanoparticles hold great potential for CDT/photothermal therapy (PTT) combined antitumor therapy and could be further explored in biomedical research.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
医学成像
✓ 已验证
DOI
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
·
2019
·
IF 3.261
Yutao Yang,Xueli Yang,Keyan Zhou,Ming Jin,Wei Li
A new near-infrared (NIR) fluorescent probe based on 2-Methylchromone was exploited for relay recognition of Cu 2+ and biothiols. The mechanism involved in complex between metal ion and probe, and subsequent displacement reaction, which make the probe can detect GSH by NIR fluorescence turn on emission. Probe showed a fluorescence band at 718 nm in PBS-EtOH (3:2, v/v, 10 mM PBS, pH 7.4) solution. Upon the addition of Cu 2+ , a large fluorescence quenching was observed due to the coordination between probe 1 and Cu 2+ . The 1 -Cu 2+ could be used to detect biothiols utilizing high affinity of biothiols with Cu 2+ . This “on-off-on” fluorescent probe was also successfully applied to image GSH in MCF-7 cells and zebrafish.
研究领域:
分析化学
·
生物化学
·
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Jin-Xiang Chen,Ying-Ke Hou,Bin Sun,Rong tian Li,Wei Men,Wen-Hua Zhang,Nuan Jia,Ming Chen,Xiaoyan Tang
Breast cancer has overtaken lung cancer to rank as the top malignant tumor in terms of incidence. Herein, gold nanostar (denoted as AuNS) is used for loading disulfide-coupled camptothecin-fluorophore prodrugs (denoted as CPT-SS-FL) to form the nanocomposite of AuNS@CPT-SS-FL (denoted as AS), which, in turn, further encapsulated with hyaluronic acid (HA) to give the final nanoplatform of AuNS@CPT-SS-FL@HA (denoted as ASH). ASH effectively carries the prodrug and targets the CD44 receptor on the surface of tumor cells. The endogenously overexpressed glutathione (GSH) in tumor cells breaks the disulfide bond to activate the prodrug and release the radiosensitizer drug camptothecin (CPT) and the fluorescent imaging reagent rhodamine derivative as fluorophore (FL). The released FL can track the precise release position of radiosensitizer camptothecin in tumor cells in real time. While the AuNS has strong X-ray absorption and deposition ability due to the high atomic coefficient of elemental Au (Z = 79). At the same time, AuNS can alleviate the tumor microenvironment (TME) hypoxia through its mild photothermal therapy (PTT). Therefore, through the multiple radiosensitizing effects of GSH depletion, high atomic coefficient of Au, and hypoxia alleviation, accompanied by the radiosensitizer camptothecin, the designed ASH nanoplatform can effectively induce strong immunogenic cell death (ICD) at the tumor site via radiosensitizing therapy combined with PTT. This work provides a new way of constructing a structurally compact and highly functionalized hierarchical system toward efficient breast cancer treatment through ameliorating TME with multiple modalities.
研究领域:
肿瘤学
·
纳米医学
·
放射治疗
·
癌症免疫疗法
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-9
·
IF 4.122
Yuan Dandan,Ding Lairong,Sun Zhaomei,Li Xuemei
Here, we report a novel magnetic resonance imaging (MRI)/fluorescence bimodal amplification platform for the detection of glutathione (GSH) on the basis of redoxable manganese dioxide (MnO 2 ) nanosheets, which can be readily applied as a DNA nanocarrier, fluorescence quencher, and intracellular GSH-activated MRI contrast agent. The binding of aptamers that absorbed on the MnO 2 nanosheets to their target can facilitating the endocytosis of target-nanoprobes. Once endocytosed, the MnO 2 nanosheets can react with cellular GSH, resulting in the disintegration of nanosheets to generate plenty of Mn 2+ ions for MRI and releases the primers which were adsorbed on the MnO 2 nanosheets. Then the rolling circle amplification (RCA) reaction was initiated to amplify the fluorescence signal. In addition, after treatment with GSH, the MnO 2 nanosheets were reduced and then most of the fluorescence was recovered. Therefore, this MnO 2 nanoprobe exhibits excellent selectivity, suggesting a potential detection platform for analyzing the glutathione level in cells.
研究领域:
生物医学工程
·
纳米技术
·
癌症研究
·
分子成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Yongfei Huang,Junping Liang,Wenbo Lu,Chenzhong Li,Zhefeng Fan
Cancer is a serious threat to human health, and it is essential to find effective methods for detecting and treating cancer. Diagnostic integration is a new strategy for cancer diagnosis and treatment that enables localized detection and treatment of tumors in a single administration and effectively reduces the toxic side effects on normal tissues. It remains a challenge for small-molecule probes to achieve multifunctionality in sensing, targeting, imaging, and therapy. Photodynamic therapy (PDT), which uses photosensitizers to generate reactive oxygen species under specific wavelengths of light to ablate tumor tissue, has demonstrated unique advantages in tumor treatment. However, the high expression of Cys/GSH in the tumor region will consume the reactive oxygen species generated by photosensitizers during PDT and reduce the therapeutic effect of the tumor. In this study, the highly expressed Cys/GSH in the tumor microenvironment was used as the activation source, and benzopyrylium salt and coumarin dyes were selected as fluorophores, with the ether bond and aldehyde group as recognition sites, to construct a near-infrared-activated Cys/GSH fluorescent probe (Bpl-O-Cou). Based on the intramolecular rearrangement mechanism and intramolecular cyclization mechanism, Bpl-O-Cou could discriminate the detection of Cys/GSH accompanied by different fluorescence emissions. Under near-infrared laser irradiation, Bpl-O-Cou + Cys/GSH could produce •OH and O2–•, leading to 4T1 cell death. In vivo experiments further illustrated the interventional role of Bpl-O-Cou in the PDT process. This study provides a new idea for the design of multifunctional probes for cancer diagnostics and therapeutics.
研究领域:
肿瘤学
·
生物化学
·
药理学
·
分子成像
·
诊疗一体化
·
光医学
✓ 已验证
DOI
PubMed
高影响因子