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JOURNAL OF NANOBIOTECHNOLOGY · 2025 ·Vol. 23 ·期 1 ·1-21 · IF 12.6

A GSH-consuming polymeric nanoparticles drives ferroptosis amplification and combines chemotherapy to amplify breast cancer treatment

Pei Mingliang,Guan Xin,Hou Xiaodong,Niu Zhiyuan,Lyu Qi,Wang Kai,Wang Shanshan,Zhang Jingkai,Ke Yun,Zhuang Shuting,Chen Jie,Xu Huixiong,Yang Fan

Currently, given variations in the abnormal tumor microenvironment (TME), significant progress has been made in the treatment of breast cancer (BC) based on TME-responsive nanosystems-mediated ferroptosis. Due to inherent deficiencies such as the limited efficacy of Fe-induced catalysis, the lack of endogenous hydrogen peroxide (H 2 O 2 ), and the overexpression of glutathione (GSH) in tumor cells, the treatment of ferroptosis is restricted. Here, this document highlighted polymeric nanoparticles with GSH resection (ssP-tHB@Fe/DOX), demonstrating significant improvements in TME responses, biocompatibility, and anti-tumor effects. Our study offers a platform for combined BC amplification therapy involving ferroptosis and DOX-induced chemotherapy, and it highlights the use of 3,4,5-trihydroxybenzaldehyde (tHB) in a Fe(III)-Fe(II) cyclic reaction to deplete GSH and enhance ferroptosis. Notably, ssP-tHB@Fe/DOX could effectively disrupt mitochondrial structure and reduce membrane potential in tumor cells, leading to decreased ATP production, depletion of GSH via multi-channel approach, inhibition of GPX4 expression, and accumulation of lipid peroxidation, thereby inducing ferroptosis enhancement to achieve BC therapy. Meanwhile, the release of the anticancer drug DOX has dual effects: it interferes with NADPH to enhance the Fe-mediated Fenton reaction and induces apoptosis in tumor cells. Moreover, RNA sequencing (RNA-seq) analysis robustly supported the anti-tumor mechanism of ssP-tHB@Fe/DOX, confirming involvement in the amino acid metabolism ferroptosis signaling pathway and the p53 signaling pathway, etc. Therefore, in this study, we thoroughly introduced the design of intelligent nanosystems, proposed methods to enhance DOX-induced apoptosis and ferroptosis, offering a novel approach for cancer treatment.

研究领域: 肿瘤学 · 生物医学工程 · 药理学
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JOURNAL OF LUMINESCENCE · 2012 · IF 2.102

Determination of rifampicin based on fluorescence quenching of GSH capped CdTe/ZnS QDs

Zhengqing Liu,Pengfei Yin,Huiping Gong,Pingping Li,Xiaodan Wang,Youqiu He

Aqueous glutathione (GSH)-capped CdTe / ZnS QDs with the diameter of 3–4   nm were synthesized. The fluorescence of CdTe / ZnS QDs at 577   nm was quenched in the presence of rifampicin (Rfp), with excitation wavelength at 350   nm. The mechanism of the interaction of CdTe / ZnS QDs with Rfp was investigated. Under the optimal conditions, the calibration plot of ln( F 0 /F ) was linear in the range 0.83–56   μg   mL −1 with concentration of Rfp, and the detection limit was 0.25   μg   mL −1 . The proposed method was successfully applied to the determination of Rfp in its commercial capsules, and satisfactory results were obtained. The recovery of the method was in the range 98.6–103.2%.

研究领域: 分析化学 · 药学
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JOURNAL OF ELECTROANALYTICAL CHEMISTRY · 2015 · IF 2.729

Electrocatalytic determination of Reduced Glutathione using rutin as a mediator at acetylene black spiked carbon paste electrode

Ying Huang,Huijie Yan,Yuejin Tong

The electrocatalytic oxidation of glutathione based on rutin as a mediator was studied at acetylene black (AB) modified carbon paste electrode (CPE). The results of cyclic voltammetric experiments showed that rutin could catalyze oxidation of GSH in PBS (pH 7.0) and the oxidation current was greatly increased by using AB-CPE compared to the nonmodified CPE. The kinetic parameters such as catalytic rate constant and diffusion coefficient were obtained using double potential step chronoamperometry. Under the optimum conditions, the electrocatalytic oxidation peak current was linear to the glutathione concentration range from 0.5   μM to 3.5   μM and 2.5   μM to 25   μM with the detection limit of 0.080   μM (S/N   =   3) by differential normal pulse voltammetry (DNPV). The proposed method has been applied to the determination of glutathione in pharmaceutical sample with satisfactory results.

研究领域: 分析化学 · 生物化学 · 电化学
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MICROCHIMICA ACTA · 2019 ·Vol. 187 ·期 1 ·1-9 · IF 5.479

A MXene of type Ti3C2Tx functionalized with copper nanoclusters for the fluorometric determination of glutathione

Shi Yu-e,Han Fei,Xie Luoyuan,Zhang Chuanchuan,Li Tianzi,Wang Henggang,Lai Wing-Fu,Luo Shaojuan,Wei Wei,Wang Zhenguang,Huang Yang

Luminescent copper nanoclusters (Cu NCs) are chosen to functionalize Ti 3 C 2 T x MXene flakes to form a new kind of nanohybrid. It was applied to the determination of glutathione (GSH) via photoluminescence (PL). The Cu NCs and MXene flakes are in close contact, and the blue PL of the Cu NCs (with excitation/emission peaks at 380/425 nm) is quenched. The addition of GSH triggers the separation of the nanohybrid. This results in the recovery of PL. GSH also promotes the PL of Cu NCs via host-guest interactions. Thus, target recognition, corresponding signal output and further magnification are accomplished in a single step. Under optimum conditions, the nanohybrid can detect GSH in the 5.0 to 100 μM concentration range and with a 3.0 μM detection limit. The assay is very specific and shows high selectivity towards metal ions, small biomolecules, amino acids, and thiol containing molecules. Luminescent copper nanoclusters are used to functionalize Ti 3 C 2 T x MXene flakes, forming a nanohybrid, which is applied to detect glutathione. Target recognition, signal output and magnification are accomplished in a single step, resulting in high selectivity.

CAS / MDL: 7664-39-3 75-59-2
研究领域: 生物化学 · 分析化学
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SENSORS AND ACTUATORS B-CHEMICAL · 2018 · IF 5.667

Acetaldehyde-modified-cystine as an enhanced fluorescent probe for intracellular glutathione imaging

Linlin Hu,Xing Wei,Jie Meng,Xiaoyan Wang,Xuwei Chen,Jianhua Wang

The development of fluorescent probes for detection of glutathione (GSH) has attracted extensive attentions due to its close association with cellular functions and diseases. Herein, a fluorescence enhancement sensing system based on acetaldehyde-modified-cystine (AMC) is reported for the detection of thiols, providing detection limits of 36 and 52 μmol L −1 for GSH and cysteine (Cys) respectively. Importantly, the fluorescence response of AMC is highly selective toward thiols with respect to the coexisting species in real biological matrixes. Considering the fact that GSH levels in cancer cells is significantly higher than those of Cys and other reducing species, the fluorescence enhancing response of AMC in cancer cells is dominated by GSH. Therefore, this provides the possibility for selective intracellular GSH imaging in living cancer cells, i.e., HeLa cells in the present study.

CAS / MDL: 128-53-0
研究领域: 生物化学 · 医学诊断 · 细胞生物学
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CHEMOSPHERE · 2017 · IF 4.208

Phytochelatins play key roles for the difference in root arsenic accumulation of different Triticum aestivum cultivars in comparison with arsenate uptake kinetics and reduction

Gao Ling Shi,Lai Qing Lou,Dao Jun Li,Zhu Bing Hu,Qing Sheng Cai

In the previous studies, we have found that arsenic (As) accumulation in roots of bread wheat ( Triticum aestivum L.) seedlings were significantly different among different wheat cultivars, and As(V) tolerant wheat cultivars have much higher capacities of root As accumulation. However, the reason for the difference remains unclear. Four wheat cultivars with high (MM45 and FM8) or low (QF1 and HM29) levels of arsenic (As) accumulation were selected to investigate the relationship between root As(V) uptake kinetics and root As accumulation. MM45 and HM29 were also used to examine As(V) reduction ability and non-protein thiol (cysteine [Cys], glutathione [GSH], and phytochelatins [PCs]) concentrations in wheat seedlings. MM45 had the lowest Michaelis–Menten constant ( K m ) and maximum influx rate ( V max ). No difference in the K m values was found among the three other cultivars. No difference in As(V) reduction capacity was observed between MM45 and HM29. GSH and PC 2 were significantly induced by 10 μM As(V) in roots of wheat seedlings, particularly in MM45. Synthesis of GSH and PCs was completely suppressed in the presence of l -buthionine sulfoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. BSO markedly decreased the As tolerance of wheat seedlings and decreased the accumulation of As in roots, but increased As accumulation in shoots. No significant difference in As concentrations was found between MM45 and HM29 under the BSO treatment. GSH and PCs are the reason why As accumulation and As(V) tolerance differ in roots of different wheat cultivars.

研究领域: 植物学 · 环境科学
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MICROCHIMICA ACTA · 2017 ·Vol. 184 ·期 7 ·1923-1931 · IF 4.58

Fluorometric determination and imaging of glutathione based on a thiol-triggered inner filter effect on the fluorescence of carbon dots

Wu Di,Li Guoliang,Chen Xuefeng,Qiu Nannan,Shi Xuexiang,Chen Guang,Sun Zhiwei,You Jinmao,Wu Yongning

The authors describe a sensitive method for determination of glutathione (GSH) that is based on a thiol-triggered inner filter effect on the fluorescence of N-doped carbon dots (N-doped CDs). N-doped CDs with a quantum yield as high as 31% were prepared by a one-pot procedure, and 5,5′-dithiobis-(2-nitrobenzoic acid) was employed as a reagent for GSH recognition. The reaction product (5-thio-2-nitrobenzoic acid; TNB) acts as an absorber of the 410-nm light used to photo-excite the N-doped CDs. Hence, the fluorescence of N-doped CDs (peaking at 510 nm) is reduced with increasing concentrations of GSH. As little as 30 nM of GSH can be detected by this method. The approach was successfully applied to (a) food analysis, (b) an investigation of an oxidative stress model, and (c) to live cells imaging. The method does not require the surface of N-doped CDs to be chemically modified, and a linkage between receptor and fluorophore is not needed. In our perception, the method may become a viable tool for the detection and imaging of thiols. Fluorescence sensing strategy for glutathione detection based on a thiol-triggered inner filter effect via new N-doped carbon dots and application to food analysis, oxidative stress study and cell imaging.

CAS / MDL: 107-15-3 99-96-7
研究领域: 分析化学 · 生物化学 · 医学检测
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NEW JOURNAL OF CHEMISTRY · 2017 ·Vol. 41 ·期 24 ·15216-15228 · IF 3.269

A novel carbon dots derived from reduced L-glutathione as fluorescent probe for the detection of the L-/D-arginine

Xiaoqing Zeng,Lei Zhang,Jidong Yang,Yuan Guo,Yunmei Huang,Haiyan Yuan,Yongsheng Xie

In this report, water-soluble carbon dots (CDs) with stable fluorescence (FL) were designed and synthesized by using environment-friendly reduced L-glutathione (GSH) as the precursor and ethylenediamine (EDA) as the passivating agent through a one-step hydro-thermal method. The CDs, with bright blue FL, had the quantum yield (QY) of 40% and showed excellent monodispersity and solubility in water. The FL intensity was remarkably enhanced when a racemic modification of L-/D-arginine (Arg) was added into the CDs solution. Therefore, the CDs could be considered as a sensitive probe for the detection of Arg. Under optimized conditions, the CDs exhibited a linear fluorescence response in the range of 3–124 μM (R2 = 0.9987) Arg with the detection limit of 2.85 × 10−8 M. In addition, no evident difference was observed when comparing the FL results of L-Arg and D-Arg. Therefore, this method could not be used in the chiral recognition of two enantiomers. Under optimum conditions, the mechanism and the reasons for the enhancement of FL were investigated. The developed method exhibited great stability, selectivity and accuracy in determining the Arg content in human urine sample and the recovery range was from 97.0% to 102.2%. Thus, our proposed method has potential application in biological molecular recognition.

研究领域: 分析化学 · 生物化学 · 医学诊断
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BIOSENSORS & BIOELECTRONICS · 2016 · IF 7.476

Fluorescence turn-on and colorimetric dual readout assay of glutathione over cysteine based on the fluorescence inner-filter effect of oxidized TMB on TMPyP

Xiangyu Jiang,Fenghua Geng,Yongxiang Wang,Jinhua Liu,Peng Qu,Maotian Xu

Quantitative fluorescence turn-on and colorimetric detection of glutathione (GSH) with rapid speed, low cost have attained much attention. Herein, we developed a sensitive fluorescence turn-on and colorimetric sensor for GSH based on the inner-filter effect (IFE), which is the first time to select oxTMB and TMPyP as the IFE absorber and fluorophore pair, respectively. The absorption band of oxTMB matches well with the emission band of TMPyP in the IFE-based fluorescent assay. In the absence of GSH, the absorption peak of oxTMB at 652   nm significantly overlaps with the emission of TMPyP, resulting in the efficient IFE and inhibition of the fluorescence of TMPyP. In the presence of GSH, the absorption intensity at 652   nm decreases, generating the recovery of the fluorescence of TMPyP. Therefore, this approach is demonstrated to be a novel candidate for detection of GSH, with high sensitivity and selectivity. The linear dynamic range for the concentrations of GSH is between 0.1   μM to 20   μM along with a limit of detection (LOD) of about 30   nM (calculated LOD as 3 σ /slope). Finally, this novel sensor was successfully applied for GSH detection in fetal calf serum , and satisfactory recovery was achieved.

研究领域: 分析化学 · 生物传感 · 医学检测
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Toxics · 2022 ·Vol. 10 ·期 8 ·429 · IF 4.472

The Response of Thiols to Cadmium Stress in Spinach (Spinacia Oleracea L.)

Ya Gao,Haipu Li,Yang Song,Fenglin Zhang,Zhaoguang Yang

The aim of this study is to examine the thiol species for the high cadmium (Cd) tolerance of spinach and provide information for the improvement of soil utilization. The spinach was cultured in aqueous solution with concentrations of Cd ranging from 1 to 9 mg/L. The time responses of glutathione (GSH) and phytochelatins (PCs, PC2-PC4) in the tissues of spinach were monitored via HPLC–MS/MS, and the concentrations of Cd in the roots, shoots and leaves were detected by ICP–OES. Data were analyzed via one-way ANOVA and Spearman correlation to assess the relationships among the types of thiols and the changes between types of thiols and Cd. As Cd stress increased, Cd concentrations in tissues also increased. The total thiol contents responded to Cd stresses with correlations r ranging from 0.394 (root), 0.520 (shoot) to 0.771 (leaf) (p< 0.01). GSH and PC3were dominant on most of the days under Cd stress. The correlationrbetween improvements in GSH and increments of Cd concentration in roots was −0.808 (p< 0.01), andrbetween changes in PC3and changes in Cd concentrations in leaves was −0.503 (p< 0.01). No correlation can be found between GSH and the subtypes of PCs in shoots, but strong positive correlations within the subtypes of PCs. Thiols can be produced in different tissues of spinach, while the shoots are only a transport tissue for GSH.Keywords:glutathione;subtypes of phytochelatin;cadmium;spinach;response

研究领域: 植物学 · 环境科学
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CHEMICAL RESEARCH IN TOXICOLOGY · 2021 · IF 3.739

Metabolic Activation of Atomoxetine Mediated by Cytochrome P450 2D6

Yutong You,Xu Wang,Kaiqi Ma,Jiaru Li,Ying Peng,Jiang Zheng

Atomoxetine (ATX) is a neurological drug widely used for the treatment of attention deficit-hyperactivity disorder. Liver injury has been documented in patients administered ATX. The mechanism of ATX’s toxic action is less clear. This study is aimed to characterize reactive metabolites of ATX in vitro and in vivo to assist our understanding of the mechanisms of ATX hepatotoxicity. A hydroxylated metabolite, along with an O-dealkylation metabolite, was found in ATX-supplemented rat liver microsome incubations. Additionally, two glutathione (GSH) conjugates and two N-acetylcysteine (NAC) conjugates were observed in rat liver microsome incubations containing ATX, NADPH, and GSH or NAC. The corresponding GSH conjugates and NAC conjugates were found in bile and urine of ATX-treated rats, respectively. Recombinant P450 enzyme incubation study demonstrated that CYP2D6 dominated the metabolic activation of ATX. The insights gained from this study may be of assistance to illuminate the mechanisms of ATX-induced hepatotoxicity.

研究领域: 药理学 · 毒理学 · 肝脏病学
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Frontiers in Chemistry · 2021 · IF 5.221

A Simple Colorimetric Assay for Sensitive Cu2+ Detection Based on the Glutathione-Mediated Etching of MnO2 Nanosheets

Tang Shurong,Liu Qiao,Hu Jie,Chen Wei,An Fengping,Xu Hui,Song Hongbo,Wang Yi-Wei

In this paper, we developed a quick, economical and sensitive colorimetric strategy for copper ions (Cu2+) quantification via the redox response of MnO2 nanosheets with glutathione (GSH). This reaction consumed MnO2 nanosheets, which acted as a catalyst for the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to a blue product (oxTMB). In the presence of Cu2+, the GSH was catalyzed to GSSG (oxidized glutathione), and the solution changed from colorless to deep blue. Under the optimum conditions, the absorption signal of the oxidized product (oxTMB) became proportional to Cu2+ concentration in the range from 10 to 300 nM with a detection limit of 6.9 nM. This detection system showed high specificity for Cu2+. Moreover, the system has been efficaciously implemented for Cu2+ detection in actual tap water samples. The layered-nanostructures of MnO2 nanosheets make it possess high chemical and thermal stability. TMB can be quickly oxidized within 10 min by the catalyzing of MnO2 nanosheets with high oxidase-like activity. There is no need of expensive reagents, additional H2O2 and complicated modification processes during the colorimetric assay. Therefore, the strategy primarily based on MnO2 nanosheets is promising for real-time, rapid and highly sensitive detection of Cu2+ under practical conditions.

研究领域: 分析化学 · 环境科学
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