JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-15
·
IF 9.429
Zhang Ruiyi,Liu Teng,Li Wanzhen,Ma Zhiyuan,Pei Pei,Zhang Weiwei,Yang Kai,Tao Yugui
Tumor microenvironment (TME), characterized by high glutathione (GSH), high hydrogen peroxide (H2O2) and acidic pH levels, is favorable for the growth, invasion and metastasis of cancer cells. Taking advantage of the specific characteristics of tumors, TME-responsive GCBD NPs are designed to deliver nanoscale coordination polymers (NCPs, GA-Cu) and chemotherapy drugs (doxorubicin, DOX) based on bovine serum albumin (BSA) nanocarriers into cancer cells for combined chemodynamic therapy (CDT) and chemotherapy. In an acidic environment, GCBD NPs could release approximately 90% copper ions, which can not only consume overexpressed GSH to modulate the TME but can also react with endogenous H2O2 in a Fenton-like reaction to achieve the CDT effect. Meanwhile, the released DOX could enter the nucleus of tumor cells and affect their proliferation to achieve efficient chemotherapy. Both in vitro and in vivo experiments showed that GCBD NPs had good biosafety and could effectively inhibit the growth of cancer cells. GCBD NPs are promising as a biocompatible nanoplatform to exploit TME characteristics for combined chemo and chemodynamic therapy, providing a novel strategy to eradicate tumors with high efficiency and specificity.Graphical Abstract
研究领域:
肿瘤学
·
纳米医学
·
生物材料学
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DOI
PubMed
高影响因子
Analytical Methods
·
2016
·Vol. 8
·期 11
·2366-2374
·
IF 1.915
Zongen Liu,Xiaohui Cai,Xuefang Lin,Yanjie Zheng,Yangting Wu,Pingping Chen,Shaohuang Weng,Liqing Lin,Xinhua Lin
Graphene quantum dots (GQDs) exhibit strong photoluminescence, biocompatibility, and low toxicity and can easily functionalize surfaces to improve the detection of biomolecules. As-prepared MnO2 nanosheets were applied in the fabrication of GQDs–MnO2 composite to develop a signal-on fluorescent platform for sensing glutathione (GSH). The fluorescence of the GQDs was quenched by MnO2 in the GQDs–MnO2 composite as a result of fluorescence resonance energy transfer within the composite. The fluorescence of GQDs was restored when GSH was introduced because GSH reduced the MnO2 nanosheets into Mn2+ and released GQDs. Under the optimized conditions, the concentration of GSH can be accurately detected with high sensitivity and specificity in Tris–HCl buffer and simulated serum. The proposed sensing strategy was successfully used to measure GSH in the range of 1–1000 μM with a detection limit of 0.45 μM. In addition, GSH in reduced glutathione injection and reduced glutathione tablets can be determined accurately using the proposed method. GQDs–MnO2 composite is thus a promising GSH fluorescence sensor for the analysis of complex systems and for quality control in the pharmaceutical industry.
研究领域:
分析化学
·
生物医学工程
·
药物分析
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产品关联
DOI
高影响因子
TALANTA
·
2022
·
IF 6.556
Shan He,Wen-Le Fang,Xiao-Feng Guo,Hong Wang
Redox homeostasis is the guarantee for the normal operation of living organisms. Given its importance, monitoring dynamic changes of redox state will facilitate the study of relevant physiological and pathological processes. Herein, a two-photon fluorescent probe NA-Se with selenomorpholine as the response site has been developed for reversible detection of redox state. NA-Se exhibits outstanding analytical performance, including a rapid response to ClO − within 8 s, a detection limit as low as 13.3 nM, and at least 10 redox reversible cycles. Furthermore, NA-Se has improved water solubility and extremely low cytotoxicity, making it ideal for bioimaging. Finally, NA-Se has been successfully applied to monitor the ClO − /GSH redox cycle in living cells and zebrafish. This work may provide an effective tool for studying redox state and related diseases in vivo.
研究领域:
生物化学
·
医学影像
·
细胞生物学
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DOI
高影响因子
BIOCONJUGATE CHEMISTRY
·
2023
·
IF 4.7
Ruibang Wu,Zheng Liu,Yong Huang,Leizhen Huang,Juehan Wang,Hong Ding,Zhe Wang,Qiujiang Li,Ce Zhu,Limin Liu,Li Zhang,Ganjun Feng
The emergence of nanozymes presents a promising alternative to antibiotics for reactive oxygen species-mediated broad-spectrum antimicrobial purposes, but nanozymes still face challenges of low therapeutic efficiency and poor biocompatibility. Herein, we creatively prepared a novel kind of hollow cobalt sulfide (CoS) nanospheres with a unique mesoporous structure that is able to provide numerous active sites for enzyme-like reactions. The results revealed that 50 μg/mL of CoS nanospheres exhibited strong peroxidase- and oxidase-like activities under physiological conditions with the assistance of a low concentration of hydrogen peroxide (H2O2, 100 μM) while possessing highly efficient GSH-depletion ability, which endowed CoS nanospheres with triple enzyme-like properties to combat bacterial infections. The in vitro experiments demonstrated that the CoS nanozyme displayed significant antibacterial effects against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). The in vivo implantation showed that the synthesized CoS effectively eliminated bacteria and promoted the recovery of infected wounds in rats while exhibiting a low cytotoxicity. This study provides a promising treatment strategy to accelerate infected wound healing.
研究领域:
生物材料学
·
医学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2019
·
IF 1.911
Zheng Zhang,Yuanhui Ji,Wei Chen
In this work, hollow manganese dioxide/gold nanoparticle (MnO 2 /GNPs) hybrid drug nanocarriers were prepared by coupling the gold nanoparticles (GNPs) with hollow structure manganese dioxide (MnO 2 ). Among them, GNPs have been used as near-infrared (NIR)-responsive element for photothermal effect under NIR laser irradiation. The glutathione (GSH)-responsive and pH-responsive performances of drug release were derived from hollow MnO 2 . Particularly, Doxorubicin hydrochloride (DOX) can be loaded into hollow MnO 2 /GNPs with the drug loading efficiency up to 82.0%. Moreover, the photothermal effect and GSH-/pH-responsive properties of hollow MnO 2 /GNPs were investigated. The hollow MnO 2 /GNPs possessed satisfactory drug release efficiency ( ca. 87.4% of loaded drug released in 12 h) and have high photothermal conversion efficiency, multiresponsive properties, and degradability. Finally, the kinetics of drug release was discussed in detail. Thus, our finding highlights that the multiresponsive nanocarriers are of great potential in the field of drug controlled release.
研究领域:
生物医学工程
·
纳米医学
·
药剂学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Lidong Gong,Changrong Wang,Pengcheng Xu,Jingjing Gong,Chuanda Zhu,Shiming Di,Yanglonghao Li,Yongxu Mu,Hongbin Han,Qiang Zhang,Zhiqiang Lin
Bioresponsive nanomaterials are increasingly important in a variety of applications such as disease imaging, drug delivery, and tissue engineering. However, it remains a big challenge to manipulate response efficacy of such materials for performance optimization in a highly complex milieu in vivo. Here, we developed chemically adjustable nanoreactors (CANs) with the structure of polymeric cores and albumin shells to achieve tunable redox responsivity. In vitro characterization demonstrates stable, spherical nanoparticles of the CANs with a particle size of about 50 nm. The fluorescence activation ratios of the CANs are determined by various albumin modification densities on the shell. Meanwhile, the response sensitivity of the CANs to GSH levels (0.6–4 mM) can be tuned by acid–base properties of polymeric blocks in the core. This unique tunable redox responsivity enables the CANs suitable for probe optimization in cancer imaging both in vivo and at histological levels. Overall, this study offers a new design strategy for manipulation on performance of core/shell nanoreactors or bioresponsive nanomaterials.
研究领域:
生物材料学
·
医学工程
·
分子影像学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2022
·
IF 5.546
Jinsheng Liu,Zhuoer Dai,Pingkai Shen,Yihua Yin,Yin Yi,Weiquan Cai,Lihong Fan,Guanghua He,Jingli Zhang,Wenjin Xu,Silin Chen,Jiayi Pan
To enhance bacteria-targeting and improve bactericidal activity, a novel GSH-responsive photodynamic antimicrobial nanosystem based on Alginate oligosaccharide-protoporphyrin IX (AOS-ss-PpIX) conjugates were constructed. The fluorescence self-quenching caused by the aggregation of PpIX groups into hydrophobic core could promote the photostability of PpIX and avoid the phototoxicity of the non-infected sites of the target plants. But once exposed to GSH stimulus, the recovery of high photodynamic activity were observed due to the destruction of the system and accompanied by the release of thiolated PpIX, and the photodynamic activity after 2 h was higher than that of PpIX under the same conditions. Furthermore the system showed more efficient photodynamic antibacterial capacity under light exposure. Moreover, the pot experiment also verified that the system showed outstanding control efficacy against cabbage soft rot caused by Erwinia carotovora Sclerotinia. Safety test exhibited that the size of nanoparticles can restrict the entry of nanoparticles into the plant cells to trigger photocytotoxicity. The design strategy provides a platform for promoting the utilization of photoactivated pesticides and reducing or avoiding their harm to target plants and the environment.
研究领域:
植物学
·
微生物学
·
农药科学
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产品关联
DOI
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 19
·6972
·
IF 4.6
Zheng Huang,Tong Xian,Xiangyi Meng,Huaisong Hu,Lixia Gao,Jiuhong Huang,Donglin Yang,Kepeng Ou,Bochu Wang,Yimei Zhang
Photodynamic therapy (PDT) is an effective noninvasive therapeutic strategy that has been widely used for anti-tumor therapy by the generation of excessive highly cytotoxic ROS. However, the poor water solubility of the photosensitizer, reactive oxygen species (ROS) depleting by high concentrations of glutathione (GSH) in the tumor microenvironment and the activation of DNA repair pathways to combat the oxidative damage, will significantly limit the therapeutic effect of PDT. Herein, we developed a photosensitizer prodrug (CSP) by conjugating the photosensitizer pyropheophorbide a (PPa) and the DNA-damaging agent Chlorambucil (Cb) with a GSH-responsive disulfide linkage and demonstrated a multifunctional co-delivery nanoplatform (CSP/Olananoparticles (NPs)) together with DSPE-PEG2000and PARP inhibitor Olaparib (Ola). TheCSP/Ola NPsfeatures excellent physiological stability, efficient loading capacity, much better cellular uptake behavior and photodynamic performance. Specifically, the nanoplatform could induce elevated intracellular ROS levels upon the in situ generation of ROS during PDT, and decrease ROS consumption by reducing intracellular GSH level. Moreover, theCSP/Ola NPscould amplify DNA damage by released Cb and inhibit the activation of Poly(ADP-ribose) polymerase (PARP), promote the upregulation of γ-H2AX, thereby blocking the DNA repair pathway to sensitize tumor cells for PDT. In vitro investigations revealed thatCSP/Ola NPsshowed excellent phototoxicity and the IC50values ofCSP/Ola NPsagainst MDA-MB-231 breast cancer cells were as low as 0.05–01 μM after PDT. As a consequence, the co-delivery nanoplatform greatly promotes the tumor cell apoptosis and shows a high antitumor performance with combinational chemotherapy and PDT. Overall, this work provides a potential alternative to improve the therapeutic efficiency of triple negative breast cancer cell (TNBC) treatment by synergistically enhancing DNA damage and disrupting DNA damage repair.Keywords:chemo-photodynamic therapy;DNA damage repair;PARP inhibitor;co-delivery;GSH-responsive
研究领域:
癌症治疗
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药学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Xin Zheng,Wei Wu,Yurou Li,Wupei Pan,Yinan Xu,Lianwei Zhong,Yinjie Jiang,Jie Zhou
Matrine (MT), an alkaloid extracted from Sophora flavescens , is widely used in traditional Chinese medicine. However, its clinical application is limited by its toxic effects. In this study, we explored the function of the activating transcription factor 4 /cystathionine γ-lyase (ATF4/CTH) pathway in MT-induced cardiac injury. Our results indicated that MT significantly decreased cysteine (Cys) and glutathione (GSH) levels, leading to mitochondrial dysfunction and apoptosis characterised by ROS accumulation, mPTP opening, ΔΨm disruption, and caspase-9/3 activation. However, caspase-3 inhibition and GSH supplementation alleviated these toxic effects. NAC similarly protected against MT-induced apoptosis by providing Cys as a substrate for GSH synthesis, whereas BSO abolished this protection by inhibiting GSH biosynthesis. Additionally, MT suppressed both ATF4 expression and its transcriptional activity, leading to reduced mRNA and protein levels of the downstream target gene CTH, and consequently diminished CTH-dependent Cys production. Overexpression of either ATF4 or CTH attenuated MT-induced apoptosis by restoring intracellular Cys and GSH levels. CTH knock-down completely abrogated the protective effects of ATF4 overexpression, whereas CTH overexpression retained its efficacy, even in the absence of ATF4. These results indicated that MT-induced suppression of the ATF4/CTH pathway causes GSH deficiency, leading to mitochondria-dependent apoptosis and cardiotoxicity.
研究领域:
毒理学
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分子生物学
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心血管研究
·
药理学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Materials Today Advances
·
2025
·
IF 8
Lingmei Li,Shuwan Li,Lin Gao,Sitong Chen,Dejin Zang,Qing Fan,Zhiyuan Lu,Teng Liu
Amphiphilic self-assembly bridges nanoscale engineering with biological functionality, forming compartmentalized nanocarriers that enable stimuli-responsive drug delivery. We engineered a glutathione (GSH)-responsive amphiphilic conjugate (POMs-SS-CPT) by covalently linking hydrophilic polyoxometalates (POMs) with hydrophobic drug camptothecin (CPT) through disulfide bonds, alongside a non-responsive carbon-bonded control (POMs-CC-CPT). Both compounds spontaneously self-assembled into vesicles in aqueous solution, enhancing cellular internalization. The GSH-responsive POMs-SS-CPT vesicles leveraged amphiphilic nanostructuring to achieve tumor-specific triggered co-release of POMs and CPT. This spatially controlled release minimized off-target toxicity while exerting potent synergistic antitumor activity. Both in vitro and in vivo studies demonstrated that POMs-SS-CPT vesicles exhibited superior antitumor efficacy and markedly inhibited tumor growth. This work establishes a novel GSH-responsive vesicular platform for efficient POM-based combination chemotherapy and elucidates critical design principles for redox-responsive delivery, providing a mechanistic framework for nanomedicine delivery systems.
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产品关联
DOI
高影响因子
PLANT CELL AND ENVIRONMENT
·
2026
·
IF 6.3
Tao Chen,Shengchun Li,Xiujie Mu,Tianzhao Yang,Lijuan Wang,Mimi Tian,Mei Yu,Long Luo,Yuanming Xie,Wei Xuan,Graham Noctor,Yi Han
Accumulating evidence shows that reversible protein S -nitrosylation is essential for H 2 O 2 homoeostasis and signalling. However, roles for denitrosylation in such oxidative signalling remain poorly understood. Here, we examined this question using the Arabidopsis catalase-defective mutant, cat2 , in which oxidative stress induces both glutathione accumulation and salicylic acid (SA) pathways. Induction of these pathways was accompanied by enhanced thioredoxin ( TRXH5 ) expression, and oxidative stress-induced activation of the SA pathway was compromised when TRXH5 expression was genetically disabled, whereas TRXH5 overexpression stimulates H 2 O 2 -triggered SA responses. Intriguingly, TRX h5 -reinforced SA responses were antagonised by glutathione (GSH) deficiency when introducing additional pad2 mutation, localised in the GLUTAMATE-CYSTEINE LIGASE gene encoding the first enzyme of glutathione biosynthesis. Further analysis revealed that the two active cysteine residues of recombinant TRX h 5 can be denitrosylated by GSH. Blocking glutathione accumulation increased more TRX h 5-SNO formation in TRXH5-YFP cat2 pad2 trxh5 than in TRXH5-YFP cat2 trxh5 . Furthermore, S -nitrosoglutathione reductase (GSNOR) was capable of physically interacting with TRX h 5, and was also required for GSH-dependent TRX h 5 denitrosylation and TRX h 5-enhanced SA responses during oxidative stress. Collectively, these data suggest that GSH/GSNOR constitutes an active denitrosylating module that works together with the canonical NADPH-dependent TRX-reducing pathway to sustain cytosolic TRX h 5 operation within the oxidative signalling framework.
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DOI
高影响因子
LANGMUIR
·
2026
·
IF 4.4
Li Sen,Wang Wentao,Chen Yizhang,Shao Qiuze,Yang Zhaoqi,Hua Dong
Non-small-cell lung cancer (NSCLC) is a lethal malignant
tumor
worldwide. Although ferroptosis offers a promising route for curcumin-mediated
non-small-cell lung cancer therapy, its efficacy is often constrained
by the robust antioxidant defense maintained by the SLC7A11/GSH/GPX4
axis, which continuously sustains cystine uptake, glutathione biosynthesis,
and GPX4-dependent lipid peroxide detoxification, thereby maintaining
cellular homeostasis. Herein, we developed a glutathione-responsive
metal–organic framework nanoplatform for the co-delivery of
curcumin and a GPX4-targeting antisense oligonucleotide (ASO). After
cellular internalization, the disulfide-bearing framework underwent
GSH-triggered disassembly, enabling synchronized release of curcumin
and ASO while depleting the intracellular GSH. Released curcumin increased
ROS accumulation and disturbed redox homeostasis, whereas ASO silenced
GPX4 expression to concurrently disable the antioxidant defense. Flow
cytometry and Western blot assays confirmed significant ROS accumulation
and SLC7A11 downregulation, which were detailed by molecular dynamics
simulations with putative binding modes. Furthermore, the nanocomposite
demonstrated robust anticancer effects in 3D multicellular tumor spheroids
with a promoted oxidative imbalance. Taken together, this coordinated
intervention disrupted the SLC7A11/GSH/GPX4 antioxidant axis, amplified
lipid peroxidation, impaired mitochondrial function, and ultimately
enhanced ferroptotic vulnerability.
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DOI
高影响因子
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