ANALYTICAL LETTERS
·
2024
·
IF 1.6
Haohua Wang,Le Ji,Yixiang Zhang,Ruotong Wang,Zheng Cao,Dong Wang,Junfeng Cheng,Chunlin Liu
Currently, the use of metal-organic framework (MOF)-based peroxidase (POD) mimics has been attempted for the development of colorimetric biothiol detection sensors. Furthermore, Ni/Co layered double hydroxides (NiCo-LDH), as sourced from MOF, have attracted increasing interest as enzyme mimics for colorimetric detection due to their low cost, adjustable layered structure, and composition. Herein, the hollow cubes of NiCo-LDH were synthesized with zeolitic imidazolate framework-67 (ZIF-67) as a sacrificial template. NiCo-LDH nanosheets were used to construct the hollow cubes with additional active sites exposed by the hollow structure. A series of experiments were conducted to confirm the superior catalytic activities of NiCo-LDH nanozymes as peroxidase (POD)-like inhibitors to horseradish peroxidase. The enzymatic kinetic constant Km values for NiCo-LDH nanozyme were 0.70 mM (H2O2) and 0.16 mM (TMB). Glutathione (GSH) was determined with a detection limit of 0.263 μM and a detection range from 5 to 60 μM. Meanwhile, the platform exhibited exceptional selectivity and stability. The mechanism and application of NiCo-LDH nanozymes were explored to promote the development of nanozymes with multi-metal active sites.
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ELECTROCHIMICA ACTA
·
2016
·
IF 4.803
Lingzhi Zhao,Liu Zhao,Yanqing Miao,Chengxiao Zhang
A highly selective method for the electrochemical detection of reduced glutathione (GSH) has been developed on the basis of the product of a reaction between GSH and catechol as the electron mediator on single-walled carbon nanotubes modified glassy carbon electrode. A polymerization-adduct ECE mechanism at SWNTs/GCE was proposed. The oxidation peak potential was −0.160 V (vs. Ag/AgCl, sat. KCl) and the oxidation peak current showed a dependence relationship with GSH concentration in the range of 1.0 ∼500.0 μM with a detection limit of 0.5 μM GSH. The developed method can discriminate GSH from other thiol species such as L-cysteine (Cys) and cysteamine hydrochloride (Cym) within their certain concentration ranges. The as-established electrochemical method has been successfully applied for the determination of GSH from the leakage of intracellular GSH contents in HeLa cells following doxorubicin-induced cell apoptosis.
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ANALYST
·
2024
·Vol. 149
·期 15
·3961-3970
·
IF 3.6
Yao Xiao,TaoMei Peng,YuXiao Luo,Lei Jiao,TaiXing Huang,He Li
Manganese dioxide (MnO2) nanosheets possess unique physical and chemical properties, making them widely applicable in various fields, such as chemistry and biomedicine. Although MnO2 nanosheets are produced using bottom-up wet chemistry synthesis methods, their scale is below the gram level and requires a long processing time, restricting their effective scale-up from laboratory to market. We report a facile, green and scalable synthesis of MnO2 nanosheets by mixing Shiranui mandarin orange juice and KMnO4 for 30 minutes. We produced more than one gram (1.095) of MnO2 nanosheets with a 0.65 nm mean thickness and a 50 nm mean lateral size. Furthermore, we established a visual colorimetric biosensing strategy based on MnO2 nanosheets for the assay of glutathione (GSH) and cardiac troponin I (cTnI), offering high sensitivity and feasibility in clinical samples. For GSH, the limit of detection was 0.08 nM, and for cTnI, it was 0.70 pg mL−1. Meanwhile, the strategy can be used for real-time analysis by applying a smartphone-enabled biosensing strategy, which can provide point-of-care testing in remote areas.
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JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Yang Li,Jing Li,Ting Yu,Hongyi Cai,Youyu Zhang,Haitao Li,Huijun Zhou,Peng Yin
The Mercury (II) ion (Hg²⁺) is a toxic heavy metal that threatens biological systems by inducing oxidative stress and disrupting the redox balance. Biothiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) are critical in maintaining redox homeostasis and are implicated in numerous physiological and pathological processes. Understanding the complex interactions between Hg²⁺ and biothiols requires molecular tools capable of simultaneous detection. Herein, we report a novel multi-signal fluorescent probe, DPC , designed with four specific recognition sites and rhodamine and coumarin fluorophores. The DPC probe enables the selective and sensitive differentiation of Mercury (II) ion (Hg²⁺), cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), with distinct fluorescence signals. DPC can detect mercury (II) ions (Hg²⁺) in water samples with a high recovery rate ranging from 90.44 % to 112.27 %. DPC was also successfully applied for real-time imaging of these species in living cells and zebrafish, revealing that Hg²⁺ induces oxidative stress, reducing cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) levels. Furthermore, detoxifying agents such as sodium selenite (Na₂SeO₃), 2,3-dimercaptopropan-1-ol (DMPC), and L-selenocysteine (Sec) restored biothiol levels, counteracting Mercury (II) ion (Hg²⁺) toxicity. These results highlight the exceptional performance of DPC for the simultaneous imaging of Mercury (II) ions (Hg²⁺) and biothiols, providing insights into their interactions and proposing a chemobiological framework for studying heavy metal toxicity and developing detoxification strategies.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yanwen Zhu,Zhaoliang Hu,Yunen Liu,Tingcai Yan,Ling Liu,Yanqun Wang,Bing Bai
Hydrogen sulfide (H 2 S), or dihydrogen sulfane (H 2 S n ), acts as a signal molecule through the beneficial mechanism of persulfidation, known as the post-translational transformation of cysteine residues to persulfides. We previously reported that Glutathione (GSH) could regulate enzyme activity through S-desulfurization or glutathionylation of residues to generate protein-SG or protein-SSG, releasing H 2 S. However, little is known about the mechanisms by which H 2 S n and GSH affect the disulfide bonds . In this study, we provide direct evidences that H 2 S n and GSH modify the sulfhydryl group on Cys272, which forms disulfide bonds in acetylcholinesterase (AChE), to generate Cys-SSH and Cys-SSG, respectively. Glutathionylation of disulfide is a two-step reaction based on nucleophilic substitution, in which the first C S bond is broken, then the S S bond is broken to release H 2 S. H 2 S n and GSH controlled self-breathing motion in enzyme catalysis by disconnecting specific disulfide bonds and modifying cysteine residues, thereby regulating AChE activity. Here, we elucidated H 2 S n and GSH mechanisms on disulfide in the AChE system and proposed a self-breathing control theory induced by H 2 S n and GSH. These theoretical findings shed light on the biological functions of H 2 S n and GSH on sulfhydryl and disulfide bonds and enrich the theory of enzyme activity regulation.
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Asian Journal of Pharmaceutical Sciences
·
2025
·
IF 11.9
Ruijie Qian,Yawen Guo,Xuemei Gao,Jianzhuang Ren,Dawei Jiang,Rui An,Ruihua Wang,Xuhua Duan,Xinwei Han
Cerenkov radiation (CR) can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy (PDT). However, insufficient luminescence intensity hinders the clinical application of CR-PDT. Here, we developed a glutathione-responsive biomimetic nanoplatform by fusing cancer cell membranes and liposomes loaded with photosensitizer hematoporphyrin monomethyl ether (HMME) and a radiation energy amplifier Eu 3+ , named HMME-Eu@LEV. Colloidal Eu 3+ converts γ-radiation and CR from radioisotopes into fluorescence to enhance anti-tumor effects. Sequential administration ensures co-localization of HMME-Eu@LEV and radiopharmaceutical 18 F-fluorodeoxyglucose (FDG) at the tumor site, triggering enhanced CR-PDT and immunogenic cell death. Our observations indicated that luminescence resonance energy transfer between Eu 3+ and HMME was efficient, and Cerenkov luminescence from Eu@LEV+FDG was approximately 5.6-fold higher in intensity than that from FDG alone. As a result, abundant ROS were generated, and macrophages in the tumor microenvironment were polarized from M2 to M1. In addition, the immunosuppressive tumor microenvironment could be reversed by promoting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes. The activated immune system effectively inhibited the growth of primary tumors and spread of distant metastases. Our work demonstrates the feasibility of CR-PDT without an external light source and the critical role of nanomaterials in personalized medicine.
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GIANT
·
2025
·
IF 4.9
Yanrong Shuai,Xiaojuan Miao,Yan Wang,Chaozheng Zhang,Yu Liu,Yuening Cao,Tingting Zhang,Jun Lu,Yilan Liu
Conventional DNA double-strand breaks (DSBs)-inducing chemotherapeutics for acute myeloid leukemia (AML) are often limited by poor solubility, non-selectivity, and drug resistance stemming from robust tumor DNA repair mechanisms. Here, we report a glutathione (GSH)-responsive, dual-targeting nano-prodrug, designated HA-FA@Etp-Olp, for efficient AML cell eradication. The HA-FA@Etp-Olp system was constructed through the conjugation of the PARP inhibitor Olaparib (Olp) with Etoposide (Etp) via a disulfide linkage, forming an Etp-Olp heterodimeric prodrug. This hydrophobic conjugate was encapsulated within a polymeric carrier composed of poly (ethylene glycol)-modified hyaluronic acid (HA) functionalized with folic acid (FA), self-assembling into well-refined nanoparticles. Exhibiting excellent circulatory stability, HA-FA@Etp-Olp achieved efficient accumulation within AML cells leveraging CD44/FR dual-receptor-mediated active targeting, followed by GSH-triggered disassembly and specific drug release in response to elevated intracellular GSH levels. Furthermore, HA-FA@Etp-Olp elicited a synergistic cytotoxic effect against AML through a dual-pronged mechanism: "DNA damage-repair blockade" cascade and significant augmentation of mitochondrial oxidative stress, effectively inducing apoptotic cell death. This strategy provides a promising targeted nanotherapeutic approach with enhanced efficacy and reduced systemic toxicity, demonstrating significant potential for the precise treatment of AML.
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RSC Advances
·
2022
·Vol. 12
·期 30
·19063-19071
·
IF 4.036
Yehong Liu,Miaoxin Chen,Gaoyang Li,Shouhong Xu,Honglai Liu
In this study, a pH/reduction dual responsive carrier containing 42nt-nucleic acid HApt based on mesoporous silica nanoparticles (MSNs) was designed. Two kinds of low molecular weight oligomeric hyaluronic acid (HA) were used to graft onto MSN for better drug encapsulation. Crosslinked MSN-HA3000gel and MSN-HA11000gel were prepared by crosslinking the HA chain through the sulfhydrylization of the carboxyl group on the HA side chain. An appropriate amount of sulfhydryl nucleic acid (HApt-SH) was added during the crosslinking reaction, which realized the targeting ability and apoptosis function to cancer cells overexpressing the HER2 receptor. Crosslinked HA had a good effect on decreasing the side effect of DOX that the drug leakage was less than 20% under a normal body environment. However, it could realize rapid and efficient drug release in a tumor environment. As to the release of HApt, it exhibited a good response to GSH. The cytotoxicity test showed that HApt contained in HAgel had a great targeting effect and significant cytotoxicity to SKBR3 cells. As a whole, this MSN-HAgel enabled the combination of gene therapy and chemotherapy, showing the synergistic effect of “1 + 1 > 2”, providing a novel idea for cancer treatments.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
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Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 48
·7859-7869
·
IF 4.872
Huiyun Wen,Haiqing Dong,Jie Liu,Aijun Shen,Yongyong Li,Donglu Shi
Intelligent nanoparticles are capable of prolonged blood circulation without leakage of the payload and fast drug release upon exposure to environmental stimuli, such as redox stimuli, and therefore are highly desirable for cancer therapy. In this study, polymeric micelles were designed and developed with a hydrophilic poly(ethylene glycol) (PEG) shell and a hydrophobic poly-L-phenylalanine (PPhe) core, linked by a redox cleavable bond, i.e. mPEG-SS-PPhe. The mPEG-SS-PPhe micelles were loaded with the anticancer drug doxorubicin (DOX) and shown an on-demand release profile in the presence of redox agents such as glutathione (GSH). Remarkably, the GSH-triggered micellar dissociation accelerated in vitro release of DOX 4.87 fold faster at 10 mM GSH than that without GSH at 12 h. An enhanced inhibitory effect of DOX-loaded mPEG-SS-PPhe micelles was achieved by improving the intracellular GSH levels. Confocal laser scanning microscopy and flow cytometric analyses of HeLa cells further confirmed that DOX accumulation was accelerated by elevating the extracellular GSH concentrations. In addition, mPEG-SS-PPhe micelles showed excellent biocompatibility on L929 and HeLa cell lines. These redox-sensitive polymeric micelles may provide more possibilities as promising carriers for on-demand drug release in a controlled manner.
研究领域:
纳米技术
·
药剂学
·
癌症治疗
·
药物递送系统
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Advanced Healthcare Materials
·
2025
·
IF 9.6
Chen-Song Huang,Chunlei Dai,Qi Liu,Si-Yun Chen,Ya-Hao Guo,Jie-Qin Wang,An-Da Zheng,Xi-Tai Huang,Jun Wu,Xiao-Yu Yin
Ferroptosis has emerged as a critical mechanism in overcoming drug resistance in various tumors; however, its role in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) has not been thoroughly explored. Additionally, the effectiveness of ferroptosis in many cancer therapies has been limited. In our study, we found that GPX4 is upregulated in gemcitabine-resistant (GR) PDAC patient tissues and cell lines. Notably, inhibiting GPX4 can reverse gemcitabine resistance in PDAC through the induction of ferroptosis, highlighting it as a potential therapeutic target. To address this, we developed a novel nanomedicine, GSH-depleted and ferroptosis-induced (FiN), designed to encapsulate and deliver the GPX4 inhibitor RSL3, resulting in a dual ferroptosis-induced nanomedicine (DFiN). In a PDAC patient-derived xenograft (PDX) mouse model exhibiting gemcitabine resistance, DFiN demonstrated significant accumulation in GR PDAC tumors, leading to a reduction in intracellular GSH levels and inhibition of GPX4. This dual action promoted lipid peroxidation and synergistically induced ferroptosis, effectively reversing gemcitabine resistance. Both in vitro and in vivo experiments confirmed that DFiN is effective in overcoming gemcitabine resistance in GR PDAC cells and PDX tumors, with minimal toxicity observed. This study presents a promising strategy for addressing drug resistance in cancer therapy.
研究领域:
肿瘤学
·
纳米医学
·
分子生物学
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癌症治疗
·
药理学
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高影响因子
Small Methods
·
2022
·Vol. 6
·期 6
·2200178
·
IF 15.367
Rui Xu,Phei Er Saw,Lei Xu
Two-dimensional (2D) nanomaterials have attracted increasing attention in cancer theranostics due to their ultrahigh specific surface area resulting in more radicals and/or reactive oxygen species (ROS) generation in chemodynamic therapy (CDT). However, their biomedical prospects are greatly limited by poor biocompatibility, low dispersion, weak stability, and the potential threat of their high immunogenicity. Moreover, rapid depletion of ROS by the high level of antioxidants (e.g., glutathione) in cancer cells severely limits the therapeutic effects of cancer CDT. Herein, a robust method is developed to improve the biomedical application of 2D nanomaterials via constructing a 2D nanomaterials delivery nanoplatform with hemoglobin-based minerals biological coat for the safe encapsulation, long blood circulation, and controlled release of 2D nanomaterials. After intravenous administration and then internalization by cancer cells, the acidic microenvironment and high concentration of H 2 O 2 can trigger rapid release of Cu-T nanoscale metal-organic frameworks (nMOFs) from Cu-T@MH. Then, the released Cu-T nMOFs with simultaneous high ROS production and GSH depletion endow the Cu-T@MH nanoplatform with enhanced cancer CDT. Besides, the fluorescence recovery of tetrakis(4-carboxyphenyl) porphyrin in Cu-T nMOFs during the GSH depletion process can accurately visualize the cancer therapeutic action.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2026
·
IF 4.8
Yunxiang Qi,Zhenghua Zhang,Xuan Wang,Haitao Long,Lumei Pu,Weibing Xu
Smart nanopesticides demonstrates excellent potential in the prevention of tomato gray mold. Herein, temperature, pH and GSH triple responsive of pyraclostrobin nanopesticide (CDC-F127-P) is fabricated base on Pluronic F127 and cinnamaldehyde-derived liposome. The maximum fungicide loading of Pyr reaches 52.9%. The particle size and zeta potential are 143 nm and + 29 mV. The release of Pyr increases from 38% to 61% after 48 h as the temperature rises from 5 °C to 35 °C. The value increases from 62% to 87% when the concentration of oxalic acid rises from 0 to 20 mM, which increases from 10% to 37% as the concentration of GSH rises from 0 to 20 mM. The EC₅₀ of CDC-F127-P is 1.96 μg/mL. The inhibition rates of CDC-F127-P for mycelial growth and spore germination are 69.3% and 73.0% at 10 μg/mL. The nucleic acid and protein leakage reaches 124.8 μg/mL and 113.5 μg/mL. A spore mortality rate of 66.4% is arrived. Mitochondrial membrane potential reduces by 96% after treatment with 2 μg/mL. The CDC-F127-P shows a hemolysis rate of 1.8% and a tomato seed germination rate of 60% at 10 μg/mL. The contact angle on the tomato leaf is 74.0 o . A solution retention capacity of 27.5 mg/cm 2 is retained after simulated rainfall. The disease inhibition rates of 64.9% and 71.0% in detached-leaf and potted-plant assays after treatment with 10 μg/mL CDC-F127-P. The triple-responsive CDC-F127-P nanopesticide offers a highly efficient and safe strategy for gray mold control and presenting a novel approach for developing green nano-pesticides.
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