INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Lanlan Zong,Haiyan Wang,Xianqiao Hou,Like Fu,Peirong Wang,Hongliang Xu,Wenjie Yu,Yuxin Dai,Yonghui Qiao,Xuefeng Wang,Qi Yuan,Xiaobin Pang,Guang Han,Xiaohui Pu
Tumor multidrug resistance (MDR) is one of the main reasons for the failure of clinical chemotherapy. Here, a bio-responsive anti-drug-resistant polymer micelle that can respond to the reductive GSH in the tumor microenvironment (TME) for delivery of HCPT was designed. A new type of polymer with anti-drug resistance and anti-tumor effect was synthesized and used to encapsulated HCPT to form reduction-sensitive micelles (PDSAH) by a thin-film dispersion method. It is demonstrated that the micelle formulation improves the anti-tumor activity and biosafety of HCPT, and also plays a significant role in reversing the drug resistance, which contributes to inhibiting the tumor growth and prolonging the survival time of H22 tumor-bearing mice. The results indicate that this nanoplatform can serve as a flexible and powerful system for delivery of other drugs that are tolerated by tumors or bacteria.
研究领域:
药学
·
癌症研究
·
纳米技术
·
药物递送系统
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Hui Tao,Hanhan Liu,Hanchen Zhang,Hong Ren,Binyu Wen,Jing Zhang,Jiaqi Du,Ziyi Cai,Zhihong Deng
Uveal melanoma (UM), a malignant tumor originating within the ocular, characterizes high metastasis and lethality among patients. Cancer stem cells (CSCs) distinguished by the c-Met protein are believed to mediate tumor metastasis in UM. However, the low bioavailability of c-Met inhibitors like Crizotilib (Criz) limits their clinical application. Herein, a GSH-responsive nanoparticle named NP @Oxa/Criz to precisely deliver Criz and Oxaliplatin (Oxa) is synthesized in this study. The dual-action mechanism of NP @Oxa/Criz inhibits the HGF/c-Met axis to prevent the nuclear translocation of β-Catenin, thereby reducing the transcription of metastasis-associated genes and undermining the stemness and metastasis of UM cells. Simultaneously, NP @Oxa/Criz induces immunogenic cell death to boost anti-tumor immunity. In vivo studies demonstrate that NP @Oxa/Criz can accumulate in tumor sites, significantly eradicating the primary UM in the ocular and suppressing the metastasis UM in the liver and peritoneal. The outcomes from this work illuminate the therapeutic mechanisms of NP @Oxa/Criz and provide a precise and potent nanotherapeutic strategy for clinical treatment and research in highly metastatic UM.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2019
·Vol. 137
·期 11
·48473
·
IF 2.188
Desheng Qi,Jiayu Wang,Yugang Qi,Jing Wen,Shu Wei,Dajun Liu,Shuangjiang Yu
In this work, we present a new type of glutathione (GSH)-responsive polyurethane-based core‑shell nanogels (RS-CS-PUNGs) with hydrophilic methoxypolyethylene glycols (mPEG) shell, which was prepared by a one-pot synthetic method. The obtained RS-CS-PUNGs not only show a good size distribution with the hydrodynamic radii around of 20 nm, but also exhibit good stability in the organic solvent. The results demonstrate that GSH (10 mM) trigger the nanogel swelling and accelerate the loaded drug release in PBS (pH = 7.4). Although the RS-CS-PUNGs loaded with DOX show a slower cellular uptake behavior than the free doxorubicin (DOX), which is likely caused by the controlled drug release property of the nanocarrier, the enhanced cellular uptake fluorescence intensity of RS-CS-PUNGs loaded with DOX is still observed compared to the control group. Both MTT and CCK-8 assay indicate that although an obvious lower initial cytotoxicity is observed compared to free DOX at 24 h postincubation, the cytotoxicity of the RS-CS-PUNGs loaded with DOX is obvious enhanced after treated 72 h, which stayed at the similar level with free DOX. Attributing to the easy preparation progress and GSH-responsive property, RS-CS-PUNGs maybe hold the potential for further application in the field of drug delivery. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137 , 48473.
研究领域:
材料科学
·
药学
·
生物医学工程
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DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xiaohuan Guo,Bingbing Cai,Qi Fang,Yanyan Chen,Yuzhu Zhou,Zhixing Liang,Changchun Wen,Yan-Cheng Liu,Hong Liang
The high level of glutathione (GSH) in tumor cells can consume reactive oxygen species (ROS), seriously affecting the efficacy of chemodynamic therapy (CDT). Although it took a great deal of effort, developing a tumor-specific CDT that efficiently depletes GSH remains a formidable challenge. Herein, we propose a pH-responsive nanocatalyst containing the active molecule norcantharidin (NCTD) and Cu 2+ for dual GSH depletion, achieving efficient GSH depletion. Due to the weakly acidic tumor microenvironment (TME), the catalyst releases NCTD and Cu 2+ in a pH-responsive manner for the synergistic therapy of chemotherapy (CT) and CDT. Both components consume GSH and subsequently produce ROS, reducing the antioxidant capacity of cancer cells while increasing oxidative stress. This disrupts cellular redox homeostasis, leading to mitochondrial dysfunction and inducing tumor cell apoptosis. This work not only develops nanomaterials with dual GSH depletion capabilities for high-efficiency CDT but also achieves synergistic CT and CDT tumor therapy with the addition of NCTD, an active ingredient of traditional Chinese medicine.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Luyao Xu,Jing Feng,Shihao Xu,Mingli Jin,Xianyue Bai,Hui Zhang,Minghui Zhu,Shengmin Lin,Jiaxing Song,Cuixia Lu
Multimodal targeted combination therapy that harnesses synergistic effects has emerged as a transformative paradigm in cancer therapy, progressively replacing traditional monotherapy. Herein, we report a tumor microenvironment (TME)-responsive multifunctional nanoplatform Cu-Ce6@DHA NPs (CCD NPs), which is self-assembled through the coordination of Cu²⁺, the antitumor drug dihydroartemisinin (DHA), and the photosensitizer chlorin e6 (Ce6). This nanoplatform enables the near-infrared-triggered combination of cuproptosis and ferroptosis for tumor treatment. Upon internalization by tumor cells, these nanoparticles undergo glutathione (GSH)-triggered disintegration, releasing their encapsulated payloads within the TME. The released Ce6 mediates potent photodynamic therapy (PDT) under laser irradiation, and DHA undergoes GSH-dependent activation to generate cytotoxic reactive oxygen species (ROS) and suppresses glutathione peroxidase 4 (GPX4), thereby amplifying ferroptotic cell death. Concurrently, the released copper ions deplete intracellular GSH and further inhibit GPX4, which exacerbates lipid peroxidation and promotes ferroptosis. Notably, the intracellular accumulation of copper ions disrupts mitochondrial metabolism by destabilizing iron-sulfur cluster (Fe-S) proteins and inducing oligomerization of lipoylated lipoylated dihydrolipoamide S-acetyltransferase (DLAT), ultimately triggering cuproptosis. Therefore, our findings establish a novel nanoplatform that simultaneously exploits metabolic vulnerabilities (via cuproptosis), redox imbalances (via ferroptosis), and photodynamic effects, providing a promising multimodal therapeutic strategy for cancer treatment.
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 5
·1-10
·
IF 5.833
He Hang,Meng Song,Li Haimin,Yang Qingyuan,Xu Ziqiang,Chen Xueqin,Sun Zhengguang,Jiang Bingbing,Li Cao
Mitochondria, as the energy factory of most cells, are not only responsible for the generation of adenosine triphosphoric acid (ATP) but also essential targets for therapy and diagnosis of various diseases, especially cancer. The safe and potential nanoplatform which can deliver various therapeutic agents to cancer cells and mitochondrial targeted imaging is urgently required. Herein, Au nanoparticles (AuNPs), mesoporous silica nanoparticles (MSN), cationic ligand (triphenylphosphine (TPP)), doxorubicin (DOX), and carbon nanodots (CDs) were utilized to fabricate mitochondrial targeting drug delivery system (denoted as CDs(DOX)@MSN-TPP@AuNPs). Since AuNPs, as the gatekeepers, can be etched by intracellular glutathione (GSH) via ligand exchange induced etching process, DOX can be released into cells in a GSH-dependent manner which results in the superior GSH-modulated tumor inhibition activity. Moreover, after etching by GSH, the CDs(DOX)@MSN-TPP@AuNPs can serve as promising fluorescent probe ( λ ex = 633 nm, λ em = 650 nm) for targeted imaging of mitochondria in living cells with near-infrared fluorescence. The induction of apoptosis derived from the membrane depolarization of mitochondria is the primary anti-tumor route of CDs(DOX)@MSN-TPP@AuNPs. As a kind of GSH-responsive mitochondrial targeting nanoplatform, it holds great promising for effective cancer therapy and mitochondrial targeted imaging. Graphical abstract
The mitochondrial targeting drug delivery system was fabricated by AuNPs, MSN, TPP, and CDs. The nanoplatform can realize redox-responsive drug delivery and targeted imaging of mitochondria in living cells to improve the therapeutic efficiency and security.
研究领域:
纳米技术
·
癌症研究
·
药学科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 8
·3277-3286
·
IF 5.251
Jun Li,Zu-E. Hu,Xian-Ling Yang,Wan-Xia Wu,Xiu Xing,Bo Gu,Yan-Hong Liu,Na Wang,Xiao-Qi Yu
Dual stimuli-responsive camptothecin polymeric prodrugs (CPT Prodrugs) with grafted structures were designed via chemoenzymatic methods and combined with doxorubicin (DOX) for synergistic drug delivery to improve anticancer efficiency. The CPT Prodrugs loaded DOX with a high efficiency through the cooperative contribution of several interaction forces. The produced amphiphilic polymeric prodrugs loaded with DOX, referred to as DOX@CPT Prodrugs, formed homogeneous spherical micelles of appropriate sizes (sub-50 nm). The DOX@CPT Prodrug micelles showed excellent stability in release experiments under in vitro physiological conditions and maintained over 80% drug loading after 4 weeks when stored at 4 °C. Under weakly acidic pH and reduced glutathione (GSH) conditions, the DOX@CPT Prodrugs with high disulfide and tertiary amine content achieved synergistic release of the two loaded drugs and biodegraded into low-molecular-weight compounds. The cell experiments confirmed that the internalization of DOX@CPT Prodrugs into cancer cells was greatly improved by nearly 30% compared with that of free drugs. Furthermore, the synergistic drug delivery system exhibited superior anticancer efficiency with highly improved cell selectivity ratios (up to 127.0%) and greatly enhanced synergistic effects (up to 23.9%) benefiting from good long-term stability, better internalization by cells and sensitive pH and GSH dual-responsivity. In addition, the DOX@CPT Prodrugs with suitable sizes and good water solubility also exhibited a greater penetrability in the case of simulating solid tumors than the free drugs. These results demonstrate the potential of DOX@CPT Prodrugs as biodegradable, dual-responsive combination therapy nanocarriers for synergistic anticancer treatment.
研究领域:
药学
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2021
·
IF 4.098
Huixue Wang,Jinya Liu,Wei Chen,Jintong Na,Yong Huang,Guiyin Li
Glypican-3 (GPC3), a heparin sulfate proteoglycan, is a potential diagnostic and therapeutic target for hepatocellular carcinoma. In this paper, a novel fluorescent aptasensor for GPC3 detection is constructed via [email protected] quantum dots–labeled GPC3 aptamer ( [email protected] Apt ) as a fluorescence probe. First, [email protected] is screened out with higher fluorescence intensity, which emits bright blue fluorescence under ultraviolet light. Then, the fluorescence-labeled [email protected] Apt probe is formed by the combination of amination GPC3 Apt and [email protected] using EDC/NHS coupled reaction. Under hydrogen bond and π-π interaction/stacking, the fluorescence of [email protected] Apt could be quenched by reductive graphene oxide (RGO) with the help of the photoinduced electron transfer and the fluorescence resonance energy transfer mechanism. In the presence of GPC3, the [email protected] Apt specifically recognizes and binds to GPC3, giving rise to the change of secondary structure of GPC3 Apt to form the GPC3/GPC3 Apt [email protected] complex, which would lead to the disintegration of the [email protected] Apt -RGO compound. Therefore, the energy transfer process is blocked and the fluorescence intensity is restored, enabling a highly sensitive response to GPC3. When the concentration of GPC3 is from 5.0 ng/mL to 150.0 ng/mL, the fluorescence recovery rate is well linearly related to GPC3 concentration with the limit of detection of 2.395 ng/mL (S/N = 3). This strategy shows recoveries from 98.31% to 101.89% in human serum samples and provides simple, fast and cheap analysis of GPC3, which suggests that it has great potential applications in clinical diagnosis for hepatocellular carcinoma.
研究领域:
生物化学
·
分子诊断
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Hao Dan-Li,Wang Ya-Jie,Yang Jia-Ying,Xie Ran,Jia Ling-Yu,Cheng Jin-Tang,Ma Hai,Tian Ji-Xiang,Guo Shan-Shan,Liu Ting,Sui Feng,Zhao Yu,Chen Yan-Jun,Zhao Qing-He
Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) is a common severe clinical syndrome in intensive care unit, may lead to a life-threatening form of respiratory failure, resulting in high mortality up to 30–40% in most studies. Nanotechnology-mediated anti-inflammatory therapy is an emerging novel strategy for the treatment of ALI, has been demonstrated with unique advantages in solving the dilemma of ALI drug therapy. Artesunate (ART), a derivative of artemisinin, has been reported to have anti-inflammatory effects. Therefore, in the present study, we designed and synthesized PEGylated ART prodrugs and assessed whether ART prodrugs could attenuate lipopolysaccharide (LPS) induced ALI in vitro and in vivo. All treatment groups were conditioned with ART prodrugs 1 h before challenge with LPS. Significant increased inflammatory cytokines production and decreased GSH levels were observed in the LPS stimulated mouse macrophage cell line RAW264.7. Lung histopathological changes, lung W/D ratio, MPO activity and total neutrophil counts were increased in the LPS-induced murine model of ALI via nasal administration. However, these results can be reversed to some extent by treatment of ART prodrugs. The effectiveness of mPEG2k-SS-ART in inhibition of ALI induced by LPS was confirmed. In conclusion, our results demonstrated that the ART prodrugs could attenuate LPS-induced ALI effectively, and mPEG2k-SS-ART may serve as a novel strategy for treatment of inflammation induced lung injury.
研究领域:
药学
·
纳米技术
·
炎症研究
·
肺医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemElectroChem
·
2022
·Vol. 9
·期 10
·e202200237
·
IF 4.782
Xiaoxiao Chen,Pu Li,Chen Luo,Chaobiao Huang
Graphical Detection mechanism of PEC sensor for detecting xanthine based on photocurrent signal changes caused by hydrogen peroxide reduction catalyzed by copper nanoclusters A photoelectrochemical (PEC) sensor combining chitosan-coated and glutathione-protected copper nanocluster (CS−GSH−CuNCs) with peroxidase-like activity and xanthine oxidase (XAO) was developed for rapid detection of xanthine. Firstly, CS−GSH−CuNCs was prepared by glutathione (GSH) reduction using chitosan (CS) as protective agent, and then was modified on titanium dioxide nanoparticles (TiO 2 NPs)/ITO electrode which was prepared by sintering titanium dioxide (TiO 2 ) on the ITO electrode surface by high temperature calcination. After excited by light at 350 nm, the photoinduced electrons from the lowest unoccupied molecular orbital (LUMO) of CS−GSH−CuNCs were transferred to the conduction band of TiO 2 , which resulted in spatial separation of electron-hole and enhancement of photocurrent signal. XAO oxidizes xanthine to produce hydrogen peroxide (H 2 O 2 ). Part of the photoinduced electrons from CS−GSH−CuNCs transferred and catalyzed the reduction of H 2 O 2 , resulting in the reduction of the photocurrent. Under optimal conditions, the PEC sensor exhibits good sensitivity and reproducibility with the limit of detection (LOD) of 6.6 nmol ⋅ L −1 and a relative standard deviation of 3.5 % for 10 replicate detections of 1.00 μmol ⋅ L −1 xanthine and the linear range of 0.04–90.0 μmol ⋅ L −1 for xanthine. Furthermore, the PEC sensor presents nice selectivity owing to its enzyme-like activity and was successfully applied to human urine, indicating its great potential for real sample analysis.
研究领域:
生物传感
·
分析化学
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Zhong Wenzhao,Guo Feng,Chen Fangman,Law Man-Kay,Lu Jun,Shao Dan,Yu Hua,Chan Ging,Chen Meiwan
Chemodynamic therapy (CDT) eradicates tumors by intratumoral catalytic chemical reaction and subsequently disrupts redox homeostasis, which shows tumor specific reactive oxygen species (ROS)-mediated therapy. However, insufficient ROS generation and high levels of glutathione (GSH) in cancer cells have limited the therapeutic efficacy of CDT. Herein, we constructed a multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced CDT. Such a sandwich-like nanoamplifier comprised layer-by-layer artesunate (AS) and calcium carbonate coatings on the surface of manganese dioxide (MnO2) nanoparticles. The nanoamplifier was disassembled under an acidic environment once accumulated into tumor sites, and subsequently released AS to replenish the intratumoral peroxide pool for ROS amplification. Besides being an AS carrier, MnO2 exhausted GSH to yield Mn2+ ions that catalyzed the overexpression of H2O2 in the tumor, further intensifying the oxidative stress and facilitating cancer cell death. Taken together, our findings not only provide a paradigm for fabricating intratumoral catalytic nanomaterials, but also present a new ROS enhancement strategy to improve anti-tumor efficacy. Our multifunctional oxidative stress nanoamplifier might broaden the future of CDT.
研究领域:
肿瘤学
·
纳米医学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IEEE SENSORS JOURNAL
·
2023
·Vol. 23
·期 16
·18142-18149
·
IF 4.3
Mengna Liang,Lili Yuan,Congying Shao,Xingqun Zheng,Qingchun Song,Zhengrong Gu,Shun Lu
Digital imaging technology provides a unique advantage for the portable on-site detection of targeted analytes. In this work, copper nanoclusters (CuNCs) based on the eggshell membrane (ESM) were combined with the photograph-taking and color recognition functions of a smartphone to build an “ON-OFF-ON” detection platform, which realized the dual visual detection of hydrogen peroxide ( $\text{H}_{{2}}\text{O}_{{2}}$ ) and glutathione (GSH). First, a red fluorescent nanocomposite membrane (GSH-CuNCs@ESM) was prepared by in situ synthesis with GSH as the protective and reducing agent. The physical characterization results confirmed its long fluorescence (FL) lifetime ( $23.77 \mu \text{s}$ ), high quantum yield (QY, 23.79%), large Stokes shift, and good stability. In addition, it is found that $\text{H}_{{2}}\text{O}_{{2}}$ has a specific response to the GSH-CuNCs@ESM, which can quench its FL. However, the FL of the quenched membrane was restored after it was put into the GSH solution. So, visual detection of $\text{H}_{{2}}\text{O}_{{2}}$ and GSH was developed based on this phenomenon integrating with a smartphone and color recognition functions. Consequently, the limit of detection (LOD) of $\text{H}_{{2}}\text{O}_{{2}}$ is as low as 63 nM when the concentration of $\text{H}_{{2}}\text{O}_{{2}}$ is between 0 and $100 \mu \text{M}$ . The LOD of GSH is as low as $1.0 \mu \text{M}$ when the concentration of GSH was between 0 and $800 \mu \text{M}$ .
研究领域:
分析化学
·
生物医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）