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Science Advances · 2020 ·Vol. 6 ·期 36 · IF 13.117

GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer

Zhanwei Zhou,Hui Wu,Ruoxi Yang,Alan Xu,Qingyan Zhang,Jingwen Dong,Chenggen Qian,Minjie Sun

The high redox level of tumor microenvironment inhibits the oxidation treatment and the immune response. Here, we innovatively develop maleimide liposome (ML) adjuvants to promote immunogenic cell death (ICD) induction and dendritic cells (DCs) maturation by glutathione (GSH) depletion for augmenting the photothermal immunotherapy of breast cancer. The ML effectively depletes the intracellular GSH and up-regulates reactive oxygen species (ROS) in both tumor cells and DCs. In tumor cells, the ROS boosted the ABTS·+ production to activate photothermal-induced ICD. In DCs, it relieved the immunosuppression, promoting DC maturation (57%) and antigen presenting. As a result of the ML assistant, the therapeutic systems improved the infiltration of CD8+ T cells to 53% in tumor tissues, eliciting strong abscopal effect and antimetastasis effect. The MLs were believed to be a superior candidate of adjuvants for enhancing immune response and cancer therapeutic efficacy.

研究领域: 癌症研究 · 免疫治疗 · 纳米技术 · 药学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS · 2025 ·Vol. 36 ·期 21 ·1-15 · IF 2.8

Highly fluorescent carbon dots-MnO2 nanosheets probe for the detection of GSH

Ni Chuyao,Xiao Jianwu,Cao Jun,Pan Jiaqi,Li Chaorong,Zheng Yingying

In order to detect glutathione (GSH), a highly fluorescent carbon dots-MnO 2 nanosheet composite sensing device was built in this work. Strongly green fluorescent carbon dots (CDs) were first created using hydrothermal technique, and the emission wavelength of CDs was 530 nm when excited by optimal excitation wave of 420 nm. CDs-MnO 2 nano fluorescent probe for GSH detection was constructed by the combination of the carbon dots and the manganese dioxide nanosheets (MnO 2 ) through electrostatic action. Fluorescence resonance energy transfer (FRET) between CDs and MnO 2 caused CDs’ fluorescence to be extinguished. With increase of the addition of MnO 2 , the system’s fluorescence intensity dropped and then stabilized. Sensing system’s fluorescence was restored by addition of GSH because GSH degraded and reduced MnO 2 into Mn 2+ ions, which caused MnO 2 nanosheets to release carbon dots subsequently. Sensing system showed strong selectivity for GSH and demonstrated a good linear relation between the fluorescence intensity and GSH concentration within 0.1 to 1 mM, and the detection limit was 1 μM. Due to the convenient preparation method of carbon dots, simple and fast detection system as well as high sensitivity, the sensing system has significant advantages and has excellent prospects in the field of fluorescence imaging and biochemical analysis.

研究领域: 分析化学 · 纳米技术 · 生物化学 · 材料科学 · 荧光成像
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JOURNAL OF THE ELECTROCHEMICAL SOCIETY · 2024 ·Vol. 171 ·期 7 ·072501 · IF 3.1

Construction of rGO and GSH Electrochemical Sensor by Electrodeposition for Naringenin Sensing

Hui-Ting Hu,Jiang-Tao Xu,Bing-Lun Li,Guo-Cheng Han,Xiao-Zhen Feng,Heinz-Bernhard Kraatz

Naringenin (NRG), a flavanone compound present in citrus fruits, has a variety of beneficial physiological active functions such as antioxidant, anti-inflammatory, and hypoglycaemic. In this study, an sensor was constructed by electrodeposition and used for the electrochemical study of NRG. Reduced graphene oxide (rGO) and glutathione (GSH) showed the ability to synergistically amplify NRG signals and possessed good linearity in the concentration range of 10.00–1200.00 μmol l−1. The linear equation is Ip = 0.0776logc + 0.9353 (R2 = 0.9901), and the limit of detection is 3.33 μmol l−1. The sensor performed well in terms of reproducibility, stability, and selectivity, which in turn enabled the detection of NRG in tomatoes. The average recovery of the sensor is 95.68% to 111.92%, with RSD less than 11.89%. The results were also verified by Ultraviolet–visible spectroscopy(UV-vis). Furthermore, density-functional theory was employed to analyse the front track of the NRG, speculating that the NRG underwent a transfer of two electrons and two protons.

CAS / MDL: 6665-86-7 117-39-5
研究领域: 生物化学 · 分析化学
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NANOTECHNOLOGY · 2024 ·Vol. 35 ·期 41 ·415102 · IF 2.9

Construction of GSH-responsive polyethyleneimine-based delivery vector for effective gene transfection

Fang Kou,Wei Wang,Xiaohong Zhu,Tian-Yan Han,Yajun Shi,Bang-Le Zhang

The rise of gene therapy has solved many diseases that cannot be effectively treated by conventional methods. Gene vectors is very important to protect and deliver the therapeutic genes to the target site. Polyethyleneimine (PEI) modified with mannitol could enhance the gene transfection efficiency reported by our group previously. In order to further control and improve the effective gene release to action site, disulfide bonds were introduced into mannitol-modified PEI to construct new non-viral gene vectors PeiSM. The degrees of mannitol linking with disulfide bonds were screened. Among them, moderate mannitol-modified PEI with disulfide bonds showed the best transfection efficiency, and significantly enhanced long-term systemic transgene expression for 72 h in vivo even at a single dose administration, and could promote caveolae-mediated uptake through up-regulating the phosphorylation of caveolin-1 and increase the loaded gene release from the nanocomplexes in high glutathione intracellular environment. This functionalized gene delivery system can be used as an potential and safe non-viral nanovector for further gene therapy.

研究领域: 基因治疗 · 药学 · 纳米技术 · 分子生物学
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BIOORGANIC CHEMISTRY · 2025 · IF 4.7

GSH-responsive paclitaxel prodrug used in chemotherapy in combination with photodynamic therapy

Qianqian Qi,Zhanyu Zhang,Dun Wang

The lack of targeting and poor solubility of anti-tumor drugs are two major limitations to the outcome of tumor therapy. To address the inherent drawbacks, we designed a novel prodrug of paclitaxel (PTX), HP-PTX. This HP-PTX prodrug contains a PEGylated heptamethylene cyanine dye (PEG-IR808–1) that was conjugated to PTX via a redox-sensitive disulfide bond. The moiety of IR808–1 acts as a tumor-targeting ligand, enabling HP-PTX not only to target tumor cells, but also to localize to mitochondria and generate ROS under 808 nm laser irradiation to wound cellular mitochondria thus exerting cytotoxic effect. Meanwhile, in vitro cellular uptake assays showed that HP-PTX possesses MCF-7 cell tumor targeting specificity which was attributed to the preferential uptake of heptamethine cyanine dye mediated by the overexpressed organic anion-transporting polypeptides (OATP) on MCF-7 cell membrane. Near-infrared in vivo imaging showed that incorporation of polyethylene glycol effectively prolonged prodrug's half-life in vivo. In addition, in vivo experiments showed that with combinational therapy strategy HP-PTX was able to kill cancer cells with high efficiency (69.52 %) without notable toxic side effects compared to PTX. These results are evidence of the potential of the tumor-targeting prodrug HP-PTX for the treatment of breast cancer.

研究领域: 肿瘤学 · 药理学 · 生物医学工程
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ACS Biomaterials Science & Engineering · 2022 · IF 5.395

GSH-Responsive and Hypoxia-Activated Multifunctional Nanoparticles for Synergetically Enhanced Tumor Therapy

Chunyang Liu,Sihan Jia,Li Tu,Peiyan Yang,Yange Wang,Sunkui Ke,Wei Shi,Shefang Ye

The integration of reactive oxygen species (ROS)-based chemodynamic therapy (CDT) and photodynamic therapy (PDT) has attracted enormous attention for synergistic antitumor therapies. However, the strategy is severely hampered by tumor hypoxia and overproduced antioxidant glutathione (GSH) in the tumor microenvironment. Inspired by the concept of metal coordination-based nanomedicines, we proposed an effective strategy for synergistic cancer treatment in response to the special tumor microenvironmental properties. Herein, we present novel metal-coordinated multifunctional nanoparticles (NPs) by the Cu2+-triggered assembly of photosensitizer indocyanine green (ICG) and hypoxia-activated anticancer prodrug tirapazamine (TPZ) (Cu-ICG/TPZ NPs). After accumulating within tumor sites via the enhanced permeability and retention (EPR) effect, the Cu-ICG/TPZ NPs were capable of triggering a cascade of combinational therapeutic reactions, including hyperthermia, GSH elimination, and Cu+-mediated •OH generation and the subsequent hypoxia-triggered chemotherapeutic effect of TPZ, thus achieving synergistic tumor therapy. Both in vitro and in vivo evaluations suggested that the multifunctional Cu-ICG/TPZ NPs could realize satisfactory therapeutic efficacy with excellent biosafety. These results thus suggested the great potential of Cu-ICG/TPZ NPs to serve as a metallodrug nanoagent for synergetically enhanced tumor treatment.

研究领域: 癌症研究 · 纳米技术 · 药学 · 治疗学
✓ 已验证 DOI PubMed 高影响因子
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Cell Death & Disease · 2022 ·Vol. 13 ·期 11 ·1-12 · IF 9.685

PNO1 inhibits autophagy-mediated ferroptosis by GSH metabolic reprogramming in hepatocellular carcinoma

Hu Xiaomeng,He Yuchao,Han Zhiqiang,Liu Wei,Liu Dongming,Zhang Xihao,Chen Lu,Qi Lisha,Chen Liwei,Luo Yi,Li Qiang,Chen Peng,Wu Qiang,Zhu Xiaolin,Guo Hua

Effective strategies for hepatocellular carcinoma, which is the second leading cause of death worldwide, remain limited. A growing body of emerging evidence suggests that ferroptosis activation is a novel promising approach for the treatment of this malignancy. Nevertheless, the potential therapeutic targets and molecular mechanisms of ferroptosis remain elusive. In this study, we found that PNO1 is a bona fide inhibitor of ferroptosis and that autophagy induced by PNO1 promotes cystine/glutamate antiporter SLC7A11 while increasing the synthesis and accumulation of intracellular glutamate. This increase is followed by an equally proportional addition in cystine uptake, which consequently enhances system Xc - activity that leads to the inhibition of ferroptosis. In the maintenance of redox homeostasis, system Xc - activated via PNO1-autophagy metabolism is responsible for maintaining cysteine for glutathione (GSH) synthesis, and the final GSH metabolic reprogramming protects HCC cells from ferroptosis. The combination of PNO1 inhibition with drugs causing ferroptosis induction, particularly sorafenib, the first-line drug associated with ferroptosis in liver cancer shows therapeutic promise in vitro and in vivo. Together, our findings indicated that PNO1 protects HCC cells from ferroptotic death through autophagy-mediated GSH metabolic remodeling, and we identified a candidate therapeutic target that may potentiate the effect of ferroptosis-based antitumor therapy.

CAS / MDL: 284461-73-0
研究领域: 肿瘤学 · 分子生物学 · 细胞生物学
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BIOMEDICINE & PHARMACOTHERAPY · 2022 · IF 7.419

Targeted chemo-photodynamic therapy toward esophageal cancer by GSH-sensitive theranostic nanoplatform

Guodong Ren,ZiCheng Wang,Yafei Tian,Jinyao Li,Yingyu Ma,Liang Zhou,Chengwu Zhang,Lixia Guo,Haipeng Diao,Lihong Li,Li Lu,Sufang Ma,Zhifang Wu,Lili Yan,Wen Liu

As the sixth leading cause of cancer death, esophageal cancer is threatening the life of people worldwide. Traditional treatments, such as surgery, chemotherapy, radiotherapy, are facing always augmented challenges including invasion, multidrug resistance (MDR), off-target toxicity. Chemo & Photodynamic synergistic therapy represents one promising strategy for improved treatment efficiency. But it is still hindered by the lack of tumor targeting, deleterious side effects, and unfavorable microenvironment for photodynamic therapy (PDT). To overcome those obstacles, one theranostic nano-assambly drug, GCDs-Ce6/Pt-EGF, was designed and fabricated. Green fluorescence carbon dots (GCDs) with the excellent optical properties, modifiability and low toxicity were prepared as drug carrier. Epidermal growth factor (EGF) was conjugated to the nano-assembly to realize tumor specific targeting. Chlorin e6 (Ce6) in the presence of laser irradiation achieved PDT by generating proapoptosis reactive oxygen species (ROS). Moreover, Ce6 incorporated into GCDs endowed the nano-assambly imaging ability and facilitate image-guided therapy. Pt(IV), cisplatin prodrug, in the nano-assambly depleted the glutathione (GSH) of tumor microenvironment when it was reduced to cytotoxicity Pt(II). Compared with single treatment, GCDs-Ce6/Pt-EGF exhibited enhanced tumor cell killing capacity and better biosafety in vitro and in vivo , especially for EGFR bearing tumor. It paved ways for developing novel theranostic agent to be potentially applied in clinic.

研究领域: 癌症治疗 · 纳米技术 · 药物科学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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DYES AND PIGMENTS · 2022 · IF 5.122

Carbon dots for real-time colorimetric/fluorescent dual-mode sensing ClO−/GSH

Huiqing Li,Zhenni Wei,Xianwei Zuo,Hongli Chen,Cuiling Ren,Yalei Dong,Xingguo Chen

Hypochlorite (ClO − ) and antioxidants have been reported closely correlated with oxidative stress and related diseases. In recent years, many probes, especially fluorescent and colorimetric probes, have been developed to detect ClO − and antioxidants. It is meaningful to develop probes which can be used to detect them in these two modes. Herein, a novel dual mode carbon dots (DM-CDs) which can rapidly respond to ClO − and antioxidants by both fluorescent and colorimetric mode were synthesized. GSH was chosen as model antioxidants to evaluate its detection performance. The fluorescence of DM-CDs can be quenched by ClO − and then recovered by GSH, so sensitive and accurate detection of ClO − and GSH can be achieved. Meanwhile, the colour variation of this system can be observed by naked eye and detected quantitatively by UV–Vis spectra. The excellent analytical performance of DM-CDs together with their good biocompatibility endow them with great feasibility in cell imaging and real-time detection of intracellular ClO − and GSH.

CAS / MDL: 88-45-9
研究领域: 分析化学 · 生物医学 · 材料科学
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POLYMER DEGRADATION AND STABILITY · 2020 · IF 4.032

Tailoring physical machinery and biodegradation properties of unsaturated polyesters through manipulation of synthesis and curing conditions

Chuanhui Gao,Sikai Wang,Jing Zhang,Yuetao Liu,Chuanxing Wang

Unsaturated polyesters, in particular unsaturated polyesters with low volatility or without styrene, are gaining increasing importance in gel coatings, adhesives and molding resins. However, the cured unsaturated polyesters are usually described as non-degradable polyesters, which will lead to environmental and safety problems. In this paper, a kind of unsaturated copolyester with different binary acid composition, named poly (butylene succinate-co-butylene itaconic) (PBISx), was synthesized. Then, a photo-curable polyester(CPBIS) which can degrade under certain conditions was obtained by thiol - ene click reaction without adding styrene curing agent. The physical properties of unsaturated polyester PBISx can be effectively controlled by changing the ratio of raw materials, such as T g from - 23.7 o C to - 45.2 o C, Xc from 38% to 14%, and T m from 109.6 °C to 74.9 °C. It was found that CPBIS completely lost its degradability in lipase when its gel rate exceeded 98%. However, CPBIS could be degraded in GSH regardless of the gel rate, and lipase resumed its degradation in the GSH/lipase mixture, and the degradation rate reached 12% at 70h, attributed to the selective degradation of C-S-C bond by GSH and the secondary degradation of ester bond by lipase.

研究领域: 材料科学 · 环境科学 · 生物学
✓ 已验证 DOI 高影响因子
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NEW JOURNAL OF CHEMISTRY · 2019 ·Vol. 43 ·期 8 ·3419-3427 · IF 3.069

Enhancement of therapeutic effect in breast cancer with a steroid-conjugated ruthenium complex

Gaochao Lv,Ling Qiu,Ke Li,Qingzhu Liu,Xi Li,Ying Peng,Shijie Wang,Jianguo Lin

A new hybrid metallic prodrug Te–S–S–NHC–Ru (Te–S–S–NHC: 17-α-[1,3-bis(4-(tert-butyl)benzyl)-4-methyl-2,3-dihydro-1H-imidazole-bis(2-diethylcarbonate)disulfide-1H-1,2,3-triazol-1-yl]-19-testosterone) was designed and synthesized by a targeting group-drug conjugate strategy with 17α-ethynyl testosterone as the carrier vector to conjugate to our previously reported ruthenium N-heterocyclic carbene complex (NHC–Ru) with a disulfide linkage. It could be applied as a GSH-induced therapeutics system with high selectivity over potential interference by various biological compounds. The anticancer activity of the new ruthenium complex was investigated in vitro and in vivo. MTT assay against progesterone receptor positive MCF-7 (PR+) and progesterone receptor negative MBA-MD-231 (PR−) human breast cancer cell lines revealed that the cytotoxicity of the PR-targeted agent was significantly higher in PR(+) than in PR(−) cells caused by the selective cellular uptake. Moreover, in vivo antitumor activity studies indicated that Te–S–S–NHC–Ru induced a smaller tumor volume and a longer survival time of tumor-bearing mice after treatment. Thus Te–S–S–NHC–Ru may be a promising ruthenium-based anti-cancer agent for the effective treatment of tumors.

研究领域: 肿瘤学 · 药物化学 · 金属有机化学
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Journal of Pharmaceutical Innovation · 2022 · IF 2.538

A Sequential Stimulus-Responsive Nanoparticle Platform for Enhanced Tumor Growth Inhibition and Efficient Drug Delivery

Sun Yu

Purpose In this study, we fabricated a nanoplatform to target tumor sites via active and passive targeting effects, thus avoiding the toxic side effects of nanocarriers and improving the efficacy of chemotherapeutic drug delivery. Methods A sequential stimulus-responsive nanoparticle that targeted the tumor microenvironment and exhibited dual sensitivity to the reduction condition and matrix metalloproteinase-9 (MMP-9) enzyme was fabricated based on a self-assembled polypeptide-paclitaxel conjugate. Results The nanoparticles (48.9 ± 2.1 nm) transformed into rod-like nanostructures (297.1 ± 3.2 nm) in the presence of MMP-9. The rod-like nanostructures were taken up by tumor cells and then sensitive bonds were broken in response to highly expressed GSH in tumor cells to release drugs. This platform showed a tumor inhibition rate of 71.8% in S180-bearing mice and a more effective tumor inhibition rate than Taxol in 4T1-bearing mice. Conclusion This platform facilitates the design of enhanced safe and efficient chemotherapy drug delivery.

研究领域: 药学 · 肿瘤学 · 纳米医学
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