NanoImpact
·
2021
·
IF 5.316
Wanjun Zhang,Jinling Gao,Lin Lu,Tsendmaa Bold,Xin Li,Shuo Wang,Zhishang Chang,Jing Chen,Xiao Kong,Yuxin Zheng,Mingliang Zhang,Jinglong Tang
Glutathione (GSH) and glutathione-S-transferases (GSTs) are two frontlines of cellular defense against both acute and chronic toxicity of xenobiotics-induced oxidative stress. The contribution of GSH and GST enzymes to signaling pathways and the regulation of GSH homeostasis play a central role in the detoxification of numerous environmental toxins and impurities. Iron oxide nanoparticles stemmed from traffic exhaust, steel manufacturing, or welding as a potential environmental pollution can lead to adverse respiratory outcomes and aggravate the risk of chronic health conditions via persistent oxidative stress. In this work, two kinds of acute exposure experiments of iron oxide (Fe 2 O 3 and Fe 3 O 4 ) nanoparticles in cells and in vivo were conducted to evaluate the GSH levels and GST activity. Our current research presented Fe 3 O 4 nanoparticles at lower concentrations (≤100 μg/ml) seem to be more toxic to the human bronchial epithelial cells as their consumption of GSH and decrease of GST activity. The catalysis activity of Fe 3 O 4 nanoparticles per se may contribute to the intracellular GSH consumption along with inhibition of glutathione-S-transferase class mu 1 and P (GSTM1 and GSTP1) active site and expression decrease of GSTM1 and GSTP1. Accordingly, the GSH consumption and decrease in GST activity directed to the further lipid peroxidation regarded as an earlier marker for toxicity evaluation of iron oxide nanoparticles, and relevant intervention may be effective for prevention of respiratory exposure induced damage from iron oxide nanoparticles.
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MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Xiaojing Yang,Yingying Wang,Jingjing Xu,Mei-Xia Zhao
In recent years, carbon dots (CDs) have shown potential applications in fluorescence tracing and imaging due to their excellent optical and chemical properties. In this work, a new type of carbon dots (Cy7-CDs) with near-infrared absorption and emission was synthesized from cyanine dyes and polyethylene glycol by hydrothermal reaction. The prepared Cy7-CDs exhibited low toxicity and excellent biocompatibility, which were applied to detect the noble metal ions Au 3+ /Hg 2+ and glutathione via the ‘on–off-on’ mode. In addition, in vivo fluorescence images demonstrated that Cy7-CDs could efficiently accumulate in the tumor. Therefore, Cy7-CDs could act as a multi-functional probe for biological sensing and tumor diagnosis.
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Molecular Catalysis
·
2020
·
IF 3.687
Caixia Cui,Hong Ming,Linjing Li,Mingjie Li,Jian Gao,Tao Han,Yunyun Wang
We report here adopting a glucose template for synthesizing mesoporous silica for enzyme in-situ immobilization. Bifunctional GSH synthetase (GSHF) and polyphosphate kinase (PPK) were selected as model system for synthesizing GSH with ATP regeneration. Results indicated that a pore size that was slightly smaller than that of enzyme was responsible for the high performance of immobilized enzyme inside mesoporous without protein leaking. Then, the cationic dopamine was used for PPK immobilization by self-polymerization. The co-immobilized enzyme activity was much higher than that of the free enzyme. The catalytic efficiency kcat/Km of co-immobilized enzyme was higher than that of the free enzyme (8.5 and 1.5 times higher for GSHF and PPK, respectively). After optimizing the reaction parameters, the co-immobilized enzymes exhibited excellent operational and storage stability, and could be re-used seven times and retained the original activity after 30 days. It is hoped that these findings will pave the way for applying enzyme co-immobilization to biocatalytic system.
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ANALYST
·
2020
·Vol. 145
·期 8
·2982-2987
·
IF 3.978
Jia Li,Yuhui Wang,Shan Sun,A-Man Lv,Kai Jiang,Yike Li,Zhongjun Li,Hengwei Lin
Herein, we report a turn-on fluorimetric nanoprobe for intracellular glutathione (GSH) imaging. The principle of this probe is designed on the basis of the selective reduction between GSH and disulfide bond-based self-crosslinked red emissive carbon dots (abbreviated as SCCDs). The nanoprobe (i.e., SCCDs) was facilely fabricated from thiol-modified carbon dots (CDs) through oxidation in the presence of H2O2, and its fluorescence was greatly reduced due to the effect of aggregation induced quenching (AIQ). However, in the presence of GSH, the SCCDs were separated into many single CDs. As a result, the fluorescence of the nanoprobe was recovered in a GSH concentration-dependent manner, which is the basis for the quantitative analysis of GSH. The nanoprobe shows excellent specificity and a linear range from 0 to 0.15 mM towards GSH with a limit of detection (LOD) of 5.7 μM. Finally, the nanoprobe was demonstrated to have extremely low cytotoxicity, and was successfully applied for monitoring the GSH level in living cells. This work would provide a promising probe for the research of GSH in cytobiology.
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Nanoscale
·
2020
·Vol. 12
·期 32
·16738-16754
·
IF 6.895
Weidong Fei,Danfei Chen,Hongxia Tang,Chaoqun Li,Weizeng Zheng,Fengying Chen,Qianqian Song,Yunchun Zhao,Yu Zou,Caihong Zheng
Ferroptosis, a cell death path induced by the generation of reactive oxygen species (ROS), will cause the accumulation of lipid peroxides (PL-PUFA-OOH) and achieve potent tumor-regression. However, glutathione (GSH)-dependent glutathione peroxidase 4 (GPx4) can reduce PL-PUFA-OOH and antagonize the ferroptosis inducing effect of ROS. Herein, folate-PEG modified dihydroartemisinin (DHA) loaded manganese doped mesoporous silica nanoparticles (described as nanomissiles) were constructed for integrating the effect of GSH exhaustion and ROS generation. After endocytosis by tumor cells, intracellular GSH triggered the degradation of nanomissiles, which allowed the simultaneous release of DHA and Fenton catalytic Mn2+ due to the redox reaction between the manganese–oxygen bonds and GSH. The degradation would lead to GSH exhaustion, activation of Mn2+-based magnetic resonance imaging (MRI), and DHA-driven ˙OH generation. The GSH-free environment inhibited the activity of GPx4 and enhanced the accumulation of PL-PUFA-OOH oxidized by ˙OH. Furthermore, the cooperative effects suppressed tumor metastasis by destroying the structure of polyunsaturated fatty acids in the cell membranes and showed potent antitumor activity. This innovative ferroptotic therapy integrating the GSH exhaustion and ROS generation will be a promising strategy for cancer therapy.
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CERAMICS INTERNATIONAL
·
2020
·
IF 3.83
Jinyue Zhang,Mingshi Jin,Yong Il Park,Longyi Jin,Bo Quan
Manganese silicate nanoparticles have recently attracted great attention due to the effectiveness of T 1 -weighted magnetic resonance imaging (MRI) contrast agents (CAs) in the mildly acidic and high glutathione (GSH) conditions of the tumor microenvironment. Herein, ultra-small hollow manganese silicate (UHMS) nanoparticles were prepared via a facile, economical, and eco-friendly method based on a hydrothermal process using small silica nanoparticles as both the silicon source and templates. The nanoparticles showed remarkable biocompatibility and dispersion stability after modification with polyethylene glycol (PEG). Owing to their ultra-high longitudinal relaxation rate (r 1 ) at low pH values and high GSH levels, the [email protected] nanoparticles have performed an excellent pH/GSH-responsive T 1 -weighted MRI. Meanwhile, the nanoparticles showed insignificant cytotoxicity in vitro and in vivo. Therefore, the [email protected] nanoparticles show promise as T 1 -MRI CAs in the tumor microenvironment and may be used to assist in clinical cancer diagnosis.
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RSC Advances
·
2017
·Vol. 7
·期 34
·21328-21335
·
IF 3.108
Rujiang Ma,Chuan Zhang,Yong Liu,Chang Li,Yanling Xu,Baoxin Li,Yunliang Zhang,Yingli An,Linqi Shi
Amphiphilic block copolymer micelles in aqueous solution have been used extensively in delivery of hydrophobic drugs with the hydrophobic core serving as the reservoir. However, encapsulation of hydrophilic drugs by polymeric micelles with hydrophobic core is relatively difficult because of the poor interaction between them. Herein, we report a novel kind of pH/GSH dual-responsive complex micelles with a hydrophilic drug loaded, via direct subcomponent self-assembly of block copolymer poly(ethyleneglycol)-block-poly(L-lysine) (PEG-b-PLys), 2-formylbenzeneboronic acid (2-FPBA) and hydrophilic 1,2-diol-containing drugs (e.g. capecitabine (CAPE)) under physiological pH 7.4 based on the synergistic formation of an iminoboronate structure. The PEG-b-PLys/2-FPBA micelles without CAPE are well-characterized in terms of micellization mechanism, size, morphology, pH- and GSH-responsiveness. Encapsulation of CAPE by forming PEG-b-PLys/2-FPBA/CAPE complex micelles via synergistic formation of the iminoboronate structure is discussed and pH- and GSH-responsive drug-release studies are carried out. The complex micelles are stable under physiological neutral conditions but could be destroyed in response to the stimuli of physiological acidic condition (pH 5.0) and/or glutathione (GSH) at pH 7.4. pH- and GSH-responsive drug-releases are successfully achieved. The drug-loaded complex micelles could be endocytosed by HepG2 cells and efficiently deliver hydrophilic drugs into them. This type of complex micelles could be used as a promising platform for the delivery of hydrophilic 1,2-diol-containing drugs.
研究领域:
材料科学
·
药学
·
生物医学工程
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DYES AND PIGMENTS
·
2018
·
IF 3.767
Han Zhang,Xiang Xia,Hong Zhao,Guo-Ning Zhang,Dao-Yong Jiang,Xing-Ying Xue,Jiao Zhang
Hydrogen sulfide (H 2 S) and biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), play critical roles in physiological and pathological processes. However, due to the challenge in sensing H 2 S and biothiols simultaneously, it is of great importance to solve this problem in biological processes. Herein, a near-infrared fluorescent probe (HZ-NBD) based on S N Ar reactions was exploited to achieve the sensitive and selective detection of H 2 S and glutathione (GSH) simultaneously in the same conditions. The design strategy was employing dicyanoisophorone based fluorescent dye as the fluorophore, the NBD moiety as a response unit and a quencher of fluorophore. The probe exhibited a low limit of detection to H 2 S (13.2 nM) and GSH (112 nM) as well as a favourable large stokes shift (112 nm). The reaction mechanism was investigated via mass spectra. What's more, owing to the advantages of low cytotoxicity, fast response and strong anti-interference ability, the probe HZ-NBD was successfully applied to bioimage H 2 S and GSH in HepG2 cells and zebrafish.
研究领域:
生物学
·
医学
·
化学
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Theranostics
·
2020
·
IF 8.579
Hongxia Tang,Chaoqun Li,Yue Zhang,Hongyue Zheng,Ying Cheng,Jingjing Zhu,Xiaojie Chen,Zhihong Zhu,Ji-Gang Piao,Fanzhu Li
Background: Glutathione (GSH), the primary antioxidant in cells, could fight against oxidative stress. Tumor cells display a higher GSH level than normal cells for coping with the hyperoxidative state, which meets the requirements of enhanced metabolism and vicious proliferation. Therefore, the consumption of GSH will lead to cell redox imbalance and impede life activities. Herein, targeted sorafenib (SFB) loaded manganese doped silica nanoparticle (FaPEG-MnMSN@SFB) was constructed, which could destroy the intracellular redox homeostasis by consuming GSH. Methods: In this study, MnMSN was prepared by an optimized one-pot Stober's method for loading SFB, and FaPEG chain was modified on the surface of MnMSN to achieve long circulation and targeted delivery. The anticancer efficacy and mechanism of the designed FaPEG-MnMSN@SFB were assessed both in vitro and in vivo. Results: FaPEG-MnMSN@SFB exhibited efficient antitumor activity by dual depleting intracellular GSH (the degradation of MnMSN would consume intracellular GSH and the SFB would inhibit the effect of X c - transport system to inhibit GSH synthesis). Moreover, disruption of redox balance would lead to apoptosis and reactive oxygen species (ROS)-dependent ferroptosis of tumor cells. Conclusion: Such a GSH-starvation therapeutic strategy would cause multi-path programmed cell death and could be a promising strategy for cancer therapy.
研究领域:
纳米技术
·
癌症研究
·
药学
·
生物医学工程
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RSC Advances
·
2019
·Vol. 9
·期 14
·7955-7960
·
IF 3.049
Hui Zhang,Lizhen Xu,Wenxiu Li,Wenqiang Chen,Qi Xiao,Jun Huang,Chusheng Huang,Jiarong Sheng,Xiangzhi Song
A lysosome-specific fluorescent probe, Lyso-AC, for biothiols was developed by incorporation of a 4-nitrophenol moiety into a coumarin dye. The Cys/Hcy-triggered substitution-rearrangement cascade, and GSH-induced substitution reaction lead to the corresponding blue emissive amino-coumarin and yellow emissive thiol-coumarin, thereby enabling Cys/Hcy and GSH detection from distinct emissions. Moreover, this probe displayed an excellent lysosome targeting property with a 0.92 Pearson's colocalization coefficient by using Neutral Red as a reference. Significantly, biological experiments indicated Lyso-AC has the potential to monitor lysosome Cys/Hcy and GSH simultaneously in living HeLa cells from distinct emissions.
研究领域:
分析化学
·
细胞生物学
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Food Quality and Safety
·
2026
·
IF 4.9
Ba Liangjie,Luo Chenglin,Wang Xiaogang,Ye Shengjie,Luo Donglan,Cao Sen
Blueberries are prone to softening and rotting shortly after harvest, which not only complicates post-harvest preservation but also significantly impairs their quality. In this study, the regulatory mechanism of thymol pre-harvest treatment on the quality and ascorbic acid-glutathione (AsA-GSH) cycle of blueberries during storage was investigated. The results demonstrated that thymol treatment impeded the decline of total flavonoids, total phenols, reducing sugars, and starch content in blueberry fruit. In addition, thymol treatment suppressed the activities of α-amylase, β-amylase, and total amylase. In addition, thymol increased the activities of ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR) and maintained high AsA and GSH contents and AsA/(AsA + DHA) and GSH/(GSH + oxidized glutathione (GSSG)) ratios in blueberries. In conclusion, thymol improved the overall postharvest antioxidant capacity of blueberries and maintained their quality by delaying the reduction of antioxidants, inducing antioxidant enzyme activities, and enhancing the metabolic activities of the AsA-GSH cycle. Therefore, thymol pre-harvest treatment can serve as an efficient and natural pre-harvest treatment agent for preserving postharvest blueberry quality, effectively maintaining the post-harvest quality of blueberries and extending their storage life.
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Materials Today Bio
·
2025
·
IF 10.2
Su Li,Qinghua Wang,Chen Su,Zhen Jia,Guoshuang Shen,Mengting Da,Rui Yang,Jiuda Zhao,Daozhen Chen
Emerging nanodrug delivery strategies seek to overcome tumor heterogeneity and enhance drug penetration in the dense matrix of solid tumors. This study presents a dual-responsive nanoplatform, poly(lactic-co-glycolic acid)-disulfide-polyethylene glycol-glutamate (PLGA-SS-PEG-Glu) loaded with Gambogic acid (GA), engineered to exploit γ-glutamyltranspeptidase (GGT) and glutathione (GSH) triggers specific to the triple-negative breast cancer (TNBC) microenvironment. Designed with Boc-L-Glutamic Acid-1-tert-butyl ester (Boc-Glu-OtBu), this nanoplatform achieves enzyme-triggered charge reversal to enhance tumor penetration, facilitating GGT-induced charge-switching and GSH-responsive GA release. In vitro, PLGA-SS-PEG-Glu@GA shows potent cytotoxicity (IC 50 = 0.80 μg/ml) against 4T1 TNBC cells, inducing apoptosis and inhibiting cell proliferation through energy-dependent, GGT-mediated endocytosis. Compensatory Nrf2/HO-1 activation mechanistically induced by GA-loaded nanoplatform ultimately potentiated mitochondrial apoptotic pathway (Bcl-2/caspase-3) initiation, promoting apoptosis. In vivo, this nanoplatform leveraged its tumor-specific enzymatic and redox microenvironment-responsive properties to achieve enhanced deep intratumoral penetration. Treatment for 2 weeks effectively suppressed primary tumor growth, while extended therapy to one month significantly inhibited the formation of pulmonary metastatic foci. This dual-responsive strategy not only elevates drug bioavailability at the tumor site but also provides a promising solution to overcome critical barriers in solid tumor drug delivery.
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