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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Rational design of cascade reaction-assisted trinal-site fluorescent probe for simultaneous discrimination of Cys, Hcy, GSH, and H2S in living cells and zebrafish

Qian Wang,Wenting Zhang,Mingzhe Cai,Yafei Ma,Ajuan Yu,Sheng Chen,Shusheng Zhang

The reactive sulfur species (RSS), in particular Cys, Hcy , GSH, and H 2 S, play an essential role in lots of critical physiological and pathological processes. To elucidate their complex interrelationships in signaling and metabolic pathways, suitable molecular tools to simultaneously distinguish Cys, Hcy , GSH, and H 2 S are urgently needed. Herein, we developed a novel cascade reaction-assisted trinal-site fluorescent probe BCS by connecting three functional fragments for simultaneously distinguishing Cys, Hcy , GSH, and H 2 S. The probe BCS exhibited red fluorescence in the absence of the four biological RSS. However, with the attendance of Cys, Hcy , GSH, and H 2 S, the probe showed different fluorescence patterns, including blue, blue/red, green/red, and no fluorescence, respectively. More importantly, based on the different RSS-induced fluorescence patterns and multi-color fluorescence imaging, probe BCS was used to discriminate and visualize all four biological RSS in both HepG2 cells and zebrafish. It is expected that probe BCS will have applications in the diagnosis and research of RSS-related diseases in the future.

✓ 已验证 DOI 高影响因子
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BRITISH JOURNAL OF HAEMATOLOGY · 2021 ·Vol. 195 ·期 2 ·267-275 · IF 6.998

Ggct (γ-glutamyl cyclotransferase) plays an important role in erythrocyte antioxidant defense and red blood cell survival

Zaoke He,Xiaoqin Sun,Shixiang Wang,Dongsheng Bai,Xiangyu Zhao,Ying Han,Piliang Hao,Xue-Song Liu

Summary The expression of GGCT (γ-glutamyl cyclotransferase) is upregulated in various human cancers. γ-glutamyl cyclotransferase enzyme activity was originally purified from human red blood cells (RBCs), but the physiological function of GGCT in RBCs is still not clear. Here we reported that Ggct deletion in mice leads to splenomegaly and progressive anaemia phenotypes, due to elevated oxidative damage and the shortened life span of Ggct −/− RBCs. Ggct −/− RBCs have increased reactive oxygen species (ROS), and are more sensitive to H 2 O 2 -induced damage compared to control RBCs. Glutathione (GSH) and GSH synthesis precursor l -cysteine are decreased in Ggct −/− RBCs. Our study suggests a critical function of Ggct in RBC redox balance and life span maintenance through regulating GSH metabolism.

研究领域: 血液学 · 分子生物学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Biodegradable Amorphous Copper Iron Tellurite Promoting the Utilization of Fenton-Like Ions for Efficient Synergistic Cancer Theranostics

Huyun Liu,Renting Jiang,Yaxuan Lu,Beibei Shan,Yu Wen,Ming Li

The major hurdles of chemodynamic therapy (CDT) are nondegradability and low-efficiency utilization of chemodynamic agents, and intracellular glutathione (GSH)-induced rapid scavenging of hydroxyl radicals (•OH). Here, a biodegradable a-CFT@IP6@BSA agent is reported for efficient cancer therapy by encapsulating amorphous copper iron tellurite nanoparticles (a-CFT NPs) into inositol hexaphosphate (IP6) and bovine serum albumin (BSA). The biggest merits of this agent are the GSH responsive degradation and amorphous structure, allowing the tumor-specific release of plenty of Cu+ ions and their high-efficiency utilization for •OH production via the Fenton-like reaction. Besides, the released Cu+ ions can deplete the intracellular GSH and thereby protect •OH from scavenging, greatly improving the CDT efficiency. Further, it is found that the a-CFT@IP6@BSA NP treatment down-regulates the levels of glutathione peroxidase 4 and BCL-2, indicating GSH depletion-associated ferroptosis and IP6-induced apoptotic death of cancer cells. Utilizing the T1/T2 dual-modal magnetic resonance imaging capability, the a-CFT@IP6@BSA NPs are demonstrated with excellent in vivo anticancer efficiency and have great potential for imaging-guided cancer treatment.

研究领域: 癌症治疗 · 纳米医学 · 生物医学工程 · 材料科学 · 放射学
✓ 已验证 DOI PubMed 高影响因子
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Biomaterials Advances · 2026 · IF 6.7

Manganese-mineralized boric acid-modified bovine serum albumin loaded on metal-organic frameworks as a pH- and GSH-responsive nanozyme for active targeted drug delivery

Chuanda Ruan,Xi Wang,Hao Guo,Yu Li,Baowen Zhang,Xueman Wei,Jian Yang,Meng Wang,Fei Tian

Nanozyme-driven chemotherapy kinetics therapy (CDT), in combination with traditional chemotherapy, is an effective approach to overcome the poor efficacy of a single chemotherapy drug in long-term treatment settings due to drug resistance. We developed a manganese-loaded boronic acid-functionalized bovine serum albumin, and loaded it onto Zeolitic imidazolate framework-8 (ZIF-8) to obtain a nanozyme PBM@ZIF-8 with excellent drug-loading capacity. The nanozyme PBM@ZIF-8 showed notable glutathione peroxidase-like and peroxidase-like activities, with high loading capacity of 10.34% with doxorubicin (DOX) and achieved pH- and glutathione (GSH)-responsive release, which is approximately three times the drug release amount in physiological conditions. Subsequently, DOX loaded PBM@ZIF-8 (PBM@ZIF-8-DOX) achieved active targeting of Hepatocellular carcinoma (HCC) by specifically binding to sialic acid receptors, accumulating extensively within HCC cells. Through catalytic reduction of intracellular GSH levels and increased reactive oxygen species levels, this nanozyme effectively kill HepG2 cells when combined with DOX chemotherapy. Additionally, we constructed an 3D HCC microsphere model to further validate the high targeting efficiency and HCC killing efficacy of the nanoparticles in vitro . In conclusion, PBM@ZIF-8 serves as an effective drug delivery platform, providing a promising strategy for multimodal treatment of HCC.

✓ 已验证 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

Design of the tumor microenvironment-multiresponsive nanoplatform for dual-targeting and photothermal imaging guided photothermal/photodynamic/chemodynamic cancer therapies with hypoxia improvement and GSH depletion

Ying Yang,Peisan Wang,Ronghua Shi,Zhou Zhao,Anjian Xie,Yuhua Shen,Manzhou Zhu

Due to the inherent defects of complex tumor microenvironment (TME), such as hypoxia and high glutathione (GSH) content, reactive oxygen species (ROS) mediated therapies, including photodynamic therapy (PDT) and chemodynamic therapy (CDT) are greatly limited. Ingenious design of a novel nanoplatform by improving and utilizing the TME to achieve effective antitumor effects has been a significant challenge. Herein, a TME-multiresponsive nanoplatform containing innovative photosensitizer (gold nanoclusters (Au NCs) protected by L-cysteine-polyacrylamide (LCPAA) hydrogels, magnetically targeted ferric oxide (Fe 3 O 4 ) and mitochondrial localized triphenylphosphine derivatives (TPP) for cancer diagnosis and treatment is reported. The combination of Fe 3 O 4 with Au NCs@LCPAA can broaden and enhance the near-infrared (NIR) absorption of the nanoplatform so that the considerable photothermal therapy (PTT)/PDT and photothermal imaging are achieved during NIR (808 nm) laser irradiation. More importantly, because Fe 3 O 4 responds to acid TME and continuously decomposes into iron ions (Fe 2+ & Fe 3+ ), the Fenton reaction induced by Fe 2+ ions and the production of oxygen (O 2 ) from hydrogen peroxide (H 2 O 2 ) catalyzed by Fe 3+ ions as well as the depletion of GSH led by the oxidation of Fe 3+ ions all can be triggered by TME rich in H 2 O 2 and GSH, which reduce the hypoxia and antioxidant capacity of tumor so as to enhance the O 2 and/or ROS-dependent PDT/CDT of Fe 3 O 4 /Au NCs@LCPAA-TPP nanoplatform. A series of in vitro and in vivo experiments have proved that through multiple regulation of TME, the as-prepared nanoplatform integrates the potential of dual-targeting, photothermal imaging as well as synergetic improved CDT/PDT/PTT.

✓ 已验证 产品关联 DOI 高影响因子
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2020 · IF 3.232

A novel “off-on-off” fluorescent-nanoprobe based on B, N co-doped carbon dots and MnO2 nanosheets for sensitive detection of GSH and Ag+

Jun Zhang,Huan Yang,Shuang Pan,Hui Liu,Xiaoli Hu

In this study, a new “off-on-off” fluorescence strategy for detecting glutathione (GSH) and silver ions (Ag + ) is presented. The constructed nanoprobe is composed of B, N co-doped carbon dots (B, N-CDs) and manganese dioxide nanosheets (MnO 2 nanosheets), where MnO 2 nanosheets serve as a kind of efficient fluorescence quencher . The sensing mechanism of the system is based on the inner filter effect (IFE) and destruction-protection strategy. The assay strategy includes three processes: fluorescence quenching of B, N-CDs by MnO 2 nanosheets, the deconstruction of MnO 2 nanosheets by GSH, the combination between GSH and Ag + . The MnO 2 nanosheets are reduced to Mn 2+ because of the addition of GSH and restoring the fluorescence intensity of the system, while the formation of the complex between GSH and Ag + inhibit the reduction of MnO 2 nanosheets on account of the addition of Ag + , leading to the decrease in fluorescence of the probe. This strategy allows the quantitative detection of GSH and Ag + with detection limit of 0.32 μmol·L −1 and 0.24 μmol·L −1 , respectively. Moreover, this approach displays good sensitivity, selectivity and broad linear range, which could be broadly applicable for practical applications.

CAS / MDL: 70-18-8 7761-88-8
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Analytical Methods · 2019 ·Vol. 11 ·期 20 ·2650-2657 · IF 2.378

An “on–off–on” fluorescent nanoprobe for recognition of Cu2+ and GSH based on nitrogen co-doped carbon quantum dots, and its logic gate operation

Yifang Gao,Huilin Zhang,Shaomin Shuang,Hui Han,Chuan Dong

Novel nitrogen co-doped carbon dots (NCDs) were synthesized as a fluorescent “on–off–on” switch for the highly sensitive and selective sensing of Cu2+ and glutathione (GSH) by a straightforward pyrolysis route. The as-prepared NCDs exhibited not only high optical stability but also superior biocompatibility and biolabeling potentials. The “on–off” process was realized by the introduction of Cu2+ on luminescent NCDs, which formed an NCDs–Cu2+ complex and quenched the fluorescence of NCDs efficiently. “Off–on” was also recovered upon addition of GSH owing to the competitive binding of GSH and Cu2+ leading Cu2+ to escape from the surface of the NCDs. The probe demonstrated high sensitivity and selectivity toward Cu2+ and GSH over other analytes, with a low detection limit of 3.62 × 10−4 μM and 6.32 × 10−4 μM, respectively. Concurrently, an “AND” logic gate was constructed based on the as-fabricated NCDs. Thanks to the highly intense emission of NCDs, the gradual quenching and restoration of their fluorescence with the addition of Cu2+ and further GSH could also be observed with the naked eye. More importantly, the probe was also extended to cellular imaging. The probe demonstrates high selectivity, repeatability, and stability, which offers a promising platform for environmental and biological sensing applications.

✓ 已验证 产品关联 DOI 高影响因子
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Analytical Methods · 2024 ·Vol. 16 ·期 29 ·4951-4959 · IF 2.7

Detection of GSH with a dual-mode biosensor based on carbon quantum dots prepared from dragon fruit peel and the T-Hg(II)-T mismatch

Weiqin Zhao,Ruichen Zhai,Qianxiao Chen,Chun Huang,Haojia Li,Youyu Zhu,Yingfeng Duan,Jie Gao

Glutathione (GSH) is commonly used as a diagnostic biomarker for many diseases. In this study, based on carbon quantum dots prepared from dragon fruit peel (D-CQDs) and the T-Hg(II)-T mismatch, a dual-mode biosensor was developed for the detection of GSH. This system consists of two single-stranded DNA (ssDNA). DNA1 was the T-rich sequence; DNA2 was attached to streptavidin-coated magnetic beads and consisted of T-rich and G-rich fragments. Due to the presence of Hg(II), the T-Hg(II)-T mismatch was formed between T-rich fragments of two ssDNA. In the presence of GSH, Hg(II) detached from dsDNA and bound with GSH to form a new complex. The G-rich fragment assembled with the hemin shed from D-CQDs to form the G-quadruplex/hemin complex. At this time, in fluorescence mode, the fluorescence of D-CQDs quenched by hemin could be restored. In colorimetric mode, after the magnetic beads separate, a visual signal could be produced by catalyzing the oxidation of ABTS using the peroxide-like activity of the G-quadruplex/hemin complex. This biosensor in both fluorescence mode and colorimetric mode had excellent selectivity and sensitivity, and the limit of detection was 0.089 µM and 0.26 µM for GSH, respectively. Moreover, the proposed dual-mode biosensor had good application prospects for detection of GSH.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Small · 2021 ·Vol. 18 ·期 9 ·2105465 · IF 13.281

An Ultrasmall Fe3O4-Decorated Polydopamine Hybrid Nanozyme Enables Continuous Conversion of Oxygen into Toxic Hydroxyl Radical via GSH-Depleted Cascade Redox Reactions for Intensive Wound Disinfection

Jiayu Xiao,Luo Hai,Yaoyao Li,Huan Li,Minhui Gong,Zefeng Wang,Zifeng Tang,Le Deng,Dinggeng He

Nanozyme-based chemodynamic therapy (CDT) for fighting bacterial infections faces several major obstacles including low hydrogen peroxide (H 2 O 2 ) level, over-expressed glutathione (GSH) in infected sites, and inevitable damage to healthy tissue with abundant nonlocalized nanozymes. Herein, a smart ultrasmall Fe 3 O 4 -decorated polydopamine (PDA/Fe 3 O 4 ) hybrid nanozyme is demonstrated that continuously converts oxygen into highly toxic hydroxyl radical (•OH) via GSH-depleted cascade redox reactions for CDT-mediated bacterial elimination and intensive wound disinfection. In this system, photonic hyperthermia of PDA/Fe 3 O 4 nanozymes can not only directly damage bacteria, but also improve the horseradish peroxidase-like activity of Fe 3 O 4 decorated for CDT. Surprisingly, through photothermal-enhanced cascade catalytic reactions, PDA/Fe 3 O 4 nanozymes can consume endogenous GSH for disrupting cellular redox homeostasis and simultaneously provide abundant H 2 O 2 for improving •OH generation, ultimately enhancing the antibacterial performance of CDT. Such PDA/Fe 3 O 4 can bind with bacterial cells, and reveals excellent antibacterial property against both Staphylococcus aureus and Escherichia coli . Most interestingly, PDA/Fe 3 O 4 nanozymes can be strongly retained in infected sites by an external magnet for localized long-term in vivo CDT and show minimal toxicity to healthy tissues and organs. This work presents an effective strategy to magnetically retain the therapeutic nanozymes in infected sites for highly efficient CDT with good biosafety.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Parasites & Vectors · 2025 ·Vol. 18 ·期 1 ·1-22 · IF 3.5

Chrysosplenetin acts as a homeostasis stabilizer with dual-function in shattering Plasmodium berghei K173 resistance to artemisinin driven by both ABC transporters and heme-ROS/GSH axis

Ji Hongyan,Huang Yutao,Tian Jingxuan,Bo Ruonan,Heng Xin,Yang Junyi,Huang Yifan,Wang Xiangyu,Tan Qingfeng,Gao Hua,Chen Linwei,Chen Jing

Background Chrysosplenetin (CHR), a polymethoxy flavonol co-occurring with artemisinin (ART) in Artemisia annua L., reverses ART resistance in Plasmodium berghei K173 potentially by downregulating intestinal P-glycoprotein (P-gp, encoded by  Mdr1a ) expression. In the present study, we further elaborated on the mechanism by comparing differences in antimalarial activity and resistance-associated molecular expression profiles between ART alone and combination therapy in blood and tissues of Mdr1a wild-type (WT) and knockout (KO) mice infected with either sensitive or resistant malarial parasites. Methods We evaluated the effects of monotherapy and combination therapy in WT and KO mice infected with sensitive and resistant P. berghei K173 strains. The mRNA expressions of multi-resistance proteins (Mrp1, 2, 4, 5) and breast cancer resistance proteins (Bcrp) were detected. Hemoglobin levels, mRNA expressions of cytokines including tumor necrosis factor-α (IFN-α), interferon-α (IFN-α), and interleukin (IL-1β) in blood and tissues, and redox balance (ROS/GSH levels), as well as gene or protein expression of signaling pathway (PI3K/AKT-mTOR and MAPK) were investigated. Results In drug-resistant mice, combination therapy maintained the highest survival (100%) and inhibition (30%) rates and the lowest parasitaemia percentage (approximately 20.0%), irrespective of Mdr1a gene status. Furthermore, combination reshaped the spatial and ART resistance-phenotypic disparities in Mrps and Bcrp mRNA expressions (with a fold change ranging from 1.35 to 38.03), ROS/GSH balance (ranging from 1.02-fold to 10.18-fold), hemoglobin levels (ranging from 1.04-fold to 1.20-fold), and cytokine profiles (ranging from 1.14-fold to 37.79-fold) induced by ART alone, which were partially dysregulated by Mdr1a deficiency. Monotherapy and combination exert oppositely regulatory effects on the PI3K/AKT-mTOR pathway in a tissue-, Mdr1a genotype-, and parasite sensitivity/resistance-dependent manner (ranging from 1.52-fold to 84.00-fold). Specifically, CHR reversed ART-induced changes via PI3K/AKT protein inhibition (ranging from 1.20-fold to 63.00-fold), which was contingent on P-gp functionality. Finally, mitogen-activated protein kinase (MAPK) pathway was involved in the antagonistic regulation between ART alone and combination therapy in a P-gp-independent manner (ranging from 1.39-fold to 16.69-fold). Conclusions The efflux pump function of P-gp is probably not a critical factor in the mechanism by which CHR reverses ART resistance. Instead, CHR acts as a homeostasis stabilizer with dual functions: it disrupts Plasmodium berghei K173 resistance to ART driven by both ABC transporters and the heme-ROS/GSH axis, in which the non-transport function of P-gp on ART is involved. Graphical

CAS / MDL: 88495-63-0
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TALANTA · 2025 · IF 6.1

A simple colorimetric and paper-based-smartphone sensing platform based on the enhanced peroxidase-like activity of Al doping Prussian blue for point-of-care detection of GSH

Ying Yang,Liuyan Wei,Weiqin You,Huisha Huang,Shuai Wang,Dandan Hou,Chujun Qin,Zhiheng Su,Mei Li

Glutathione (GSH) is a very important antioxidant and also participates in many important physiological processes, accurate determination of GSH in food and blood fluid is crucial for human health. Herein, we introduce a simple colorimetric and paper-based-smartphone dual signal output platform for point-of-care (POC) detection of GSH in garlic and human serum. The experiment revealed that the peroxidase-like activity of Aluminum-doped Prussian blue (AlPB) could be enhanced by the doping of Al element on Prussian blue. AlPB exhibited excellent peroxidase-like activity and efficiently catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H 2 O 2 to generate blue oxidized TMB, resulting in an absorbance and color-based-smartphone dual signal readouts. Enzyme kinetic studies also indicated that the AlPB showed high affinity towards TMB. Hence, a reliable colorimetric and color-based-smartphone dual signal readouts assay was constructed based on AlPB-mediated the peroxidase-like activity, it was used for highly sensitive colorimetric and POC detection of GSH in food and human serum within 7 min with a wide range of linear response from 1 to 20 μM, a low detection limit of 0.1748 μM. This work demonstrates a novel and versatile strategy to develop superior peroxidase mimics and holds great potential for rapid and portable detection of GSH in food, healthcare and clinical diagnosis, and also open promising avenues for more powerful paper-based POC tests.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY · 2017 · IF 2.313

Dynamic responses of antioxidant enzymes in pearl oyster Pinctada martensii exposed to di(2-ethylhexyl) phthalate (DEHP)

Nan Xiang,Chunfeng Zhao,Xiaoping Diao,Qian Han,Hailong Zhou

Di(2-ethylhexyl) phthalate (DEHP) is recognized as one of the most ubiquitous contaminants in marine environments and causes adverse effects on the health of marine organisms. The purpose of this study was to investigate the toxic effects of DEHP on the pearl oyster Pinctada martensii . The Pinctada martensii was exposed to 0.0, 0.5, 2, 8, or 32   mg   L −1 DEHP for 7 and 10   days using parameters of antioxidant. Antioxidant indicators included levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), peroxidase (POD), and total antioxidant capacity (T-AOC) in the gills and hepatopancreas of Pinctada martensii for 7 and 10   days. Besides, we used the lowest observed effect concentration (LOEC) of five enzyme activities in different tissues of Pinctada martensii for 7 and 10   days to compare sensitivity. The results showed that the gills were more sensitive than the hepatopancreas of Pinctada martensii and that GSH activity in the gills and CAT activity in the hepatopancreas might be suitable biomarkers after 7   days of DEHP exposure. After 10   days of DEHP exposure, the GSH activity and CAT activity in the gills and SOD activity in the hepatopancreas could be regarded as biomarkers. Compared to the LOEC, GSH activity in the gills and CAT activity in the hepatopancreas after 7   days of DEHP exposure were more sensitive than any other biomarkers. In addition, after 10   days of DEHP exposure, GSH activity in the gills and hepatopancreas were much more sensitive than other activities. In conclusion, GSH activity demonstrated its potential to be used as a biomarker for the monitoring of DEHP pollution in the marine environment.

研究领域: 海洋生物学 · 环境毒理学 · 生态毒理学
✓ 已验证 DOI PubMed 高影响因子
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