Nanoscale
·
2024
·
IF 5.8
Jingjing Jiang,Qiong Zhang,Yue Zhang,Lintong Gao,Yan Feng,Xianshun Sun,Junjun Wang,Xiao-Jiao Zhu,Xingxing Chen,Hong-Ping Zhou
Currently, cuproptosis mainly focuses on the Cu2+ induced morphology of mitochondria (Mito), the observation of endoplasmic reticulum (ER)-related Cu2+ content in cuproptosis is relatively lacking. Herein, we develop a hydroxyflavone (HF) based NIR excited fluorescent probe, BHCO, for exhibiting specific recognition of Cu2+. BHCO can accurately locate in ER and detect Cu2+ content in cuproptosis process. The two-photon fluorescence nature of BHCO enables to track both ferroptosis and cuproptosis processes with high resolution. Furthermore, BHCO can upgrade reactive oxygen species (ROS) under 720 nm excitation, which facilitates ferroptosis occurrence. We firmly convince the nonlinear optical (NLO) small molecules could provide a valid tool for rapid tumors elimination through synergistic ferroptosis and cuproptosis.
研究领域:
生物化学
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肿瘤学
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光学成像
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Junmin Qian,Abdalrheem Jarelnaby Musa Aldai,Weijun Xu,Taibing Wang,Kunkun Zhao,Yaping Wang,Jingjing Fan,Aili Suo
Cuproptosis shows great prospects in cancer treatments. However, insufficient intracellular copper amount, low-level redox homeostasis, and hypoxic tumor microenvironment severely restrict cuproptosis efficacy. Herein, hydrazided hyaluronan-templated decorated CuO 2 -doxorubicin (CuDT) nanodot clusters (NCs) are developed for efficient doxorubicin (DOX)-sensitized cuproptosis therapy in breast cancer via a three-pronged strategy. The CuDT NCs with an average size of 56.2 nm are fabricated from 3,3′-dithiobis(propionohydrazide)-conjugated hyaluronan, Cu 2+ , and DOX through a one-pot mineralization process. The CuDT nanoparticles exhibit pH-responsive H 2 O 2 , Cu 2+ , and DOX release profiles and catalytic activity. Upon entrance into tumor cells, CuO 2 -based exogenous H 2 O 2 supply and DOX-augmented endogenous H 2 O 2 generation jointly elevate intracellular H 2 O 2 level, which can further be transformed into hydroxyl radicals and O 2 through Fenton-like reaction to achieve oxidative stress amplification and hypoxia relief, respectively. Moreover, the CuDT NCs can efficiently deplete intracellular overexpressed glutathione via Cu 2+ /Cu + cycle and abundant disulfide bonds, further enhancing cellular oxidative stress. These results demonstrate that the novel CuDT NCs achieve DOX-sensitized cuproptosis in breast cancer cells through elevating copper level, amplifying oxidative stress and alleviating hypoxia, and display prominent in vivo antitumor efficacy. Such a three-pronged strategy of targetedly boosting cuproptosis in cancer cells represents a novel approach for antitumor treatments.
研究领域:
肿瘤学
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药理学
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纳米医学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2026
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IF 11.5
Pi Zhao,Zhaokai Wang,Kedong Liu,Tong Wu,Jingyi Yang,Zixin Luo,Tianyu Zhang,Xingzhu Wang,Tao Wan
Lung cancer immunotherapy remains limited by the immunosuppressive tumor microenvironment (TME) and insufficient immunogenicity. Accumulating evidence indicates that tumor-derived exosomes (TDEs) play a pivotal role in shaping the immunosuppressive TME. Consequently, therapeutic strategies targeting TDE biogenesis and secretion offer a promising strategy to counteract tumor immune evasion. To this end, we developed an adenosine triphosphate (ATP)-responsive zeolitic imidazole framework-90 (ZIF-90)-based nanoplatform for the co-delivery of the exosome biosynthesis inhibitor GW4869 and the copper ionophore elesclomol (ES-Cu, a cuproptosis inducer). GW4869-mediated TDEs suppression alleviated immunosuppression and enhanced T-cell infiltration while simultaneously inducing reactive oxygen species (ROS) production to deplete glutathione (GSH). This GSH depletion potentiated ES-Cu-induced cuproptosis, and in combination with TDEs inhibition-mediated immunostimulation, established a positive feedback loop that remodels the TME to enhance antitumor immune responses. To our knowledge, this biomimetic nanoplatform presents an unexplored integration of exosome blockade with cuproptosis induction, establishing a novel paradigm for cancer immunotherapy.
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DOI
PubMed
高影响因子
CANCER LETTERS
·
2026
·
IF 11.8
Hui Wang,Yu Zhang,Dinghua Liu,Chang Liu,Shuang Wu,Zhuoyao Wu,Tianming Cui,Gongyao Yu,Yan Xu,Weitao Yang,Bingbo Zhang
The Warburg effect drives cancer cells to rely preferentially on glycolysis, resulting in diminished mitochondrial oxidative phosphorylation (OXPHOS). This metabolic phenotype limits the ability of excess copper (Cu) ions to trigger cuproptosis in dysfunctional mitochondria, leading to suboptimal therapeutic outcomes. Therefore, remodeling tumor energy metabolism to counteract the Warburg effect represents a pivotal strategy to enhance cuproptosis efficacy. Herein, we developed a Cu(I)-stabilized metal-organic framework nanoplatform (CuTz-1) encapsulated by Azurin (CuTz-1@Azurin) as a cuproptosis sensitizer. Mechanistically, Azurin increases p53 protein levels by intercepting MDM2-mediated ubiquitin-proteasome degradation. Elevated p53 subsequently inhibits pyruvate kinase M2 (PKM2) activity, suppressing glycolysis, while simultaneously promoting mitochondrial OXPHOS—collectively shifting cellular metabolism from glycolysis toward mitochondrial respiration and sensitizing tumor cells to Cu-induced proteotoxic stress. In addition, CuTz-1@Azurin triggers oxidative stress via reactive oxygen species (ROS) generation and glutathione (GSH) depletion, which act together with p53-mediated apoptosis to suppress tumor growth. Meanwhile, the oxidation of Cu(I) to paramagnetic Cu(II) enables real-time monitoring of the therapeutic process by magnetic resonance imaging (MRI). Both in vitro and in vivo results demonstrate good antitumor performance of CuTz-1@Azurin. This study highlights the potential of Azurin-mediated metabolic regulation as a promising strategy to potentiate cuproptosis for combined cancer therapy.
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DOI
高影响因子
ACS Applied Bio Materials
·
2025
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IF 4.7
Jie Ma,Xinhao Dang,Yan Xue,Zihuan Yin,Yi Sheng,Ruixing Luo,Xueying Zhu,Kangliang Sheng,Shan Gao,Renquan Zhang
Nanocatalysts hold significant promise in tumor therapy by facilitating the production of reactive oxygen species (ROS) within the tumor microenvironment (TME). Among these, single-atom nanozymes (SAzymes) stand out due to their atomically dispersed active sites, offering a viable alternative to natural enzymes. SAzyme can simulate the catalytic mechanisms of natural enzymes, such as peroxidase and catalase, achieving highly efficient biocatalytic effects. Moreover, they can maintain high catalytic activity and structural stability under extreme conditions. However, the application of SAzymes in anticancer treatments is still in its initial stages, necessitating further research and development. In this study, we have synthesized a single-atom catalytic enzymes with V2O5 coordination (vanadium-based single-atom catalysts, V-SAC) utilizing the electrospinning technique to enhance tumor suppression. The V-SAC demonstrates notable dual enzymatic activities, mimicking both peroxidase and glutathione peroxidase functions. It catalyzes the conversion of endogenous H2O2 to ·OH within the acidic tumor microenvironment, while simultaneously depleting glutathione (GSH). Significantly, V-SAC induces cuproptosis/ferroptosis/apoptosis, which further augments the efficacy of tumor treatment. Additionally, the exceptional photothermal properties of V-SAC enable photothermal therapy (PTT) for tumors. In vivo experiments reveal that V-SAC exhibits excellent antitumor capabilities coupled with high safety, underscoring its substantial potential for clinical applications in cancer treatment. These findings highlight the development of high-performance, biological safety single-atom catalysts for biomedical applications in tumor therapy.
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
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IF 13.2
Xuya Yu,Yushi Zhang,Zhuona Rong,Xueping Li,Lingpeng Luo,Lu Zhang,Liyu Sun,Yayue Liu,Wen Li,Lin Mei,Feng Lv,Xiaocong Pang,Qingqing Xiong
Cuproptosis, a copper-dependent form of programmed cell death, has emerged as a promising strategy to activate anti-tumor immunity through immunogenic cell death (ICD). However, its efficacy is often hindered by insufficient copper accumulation and glutathione-mediated copper chelation in tumor cells. Herein, we present an NK cell membrane-camouflaged copper‑boron dipyrrolylmethyl (BODIPY) coordinated nanoassembly to facilitate the tumor-targeted delivery of copper and integrate dual-wavelength phototherapy to potentiate cuproptosis and enhance antitumor immunity for synergistic cancer therapy. The nanoplatform enables 658 nm laser-triggered photodynamic therapy (PDT) to generate reactive oxygen species and 1064 nm laser-induced mild photothermal therapy (PTT) to produce localized hyperthermia. The combined PDT/PTT treatment not only produces direct cytotoxicity against tumor cells, but also depletes intracellular glutathione through oxidative stress, preventing copper chelation to amplify cuproptosis. This multimodal approach triggers robust ICD, driving dendritic cell maturation, macrophage polarization, tumor-infiltrating lymphocyte activation and pro-inflammatory cytokines secretion. Consequently, the immunosuppressive tumor microenvironment is remodeled, eliciting a strong and durable anti-tumor immune response that effectively inhibits tumor growth and prevents tumor recurrence and metastasis. Overall, this study proposes a novel strategy to potentiate cuproptosis-mediated ICD for synergistic cancer therapy.
研究领域:
纳米医学
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癌症免疫治疗
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光疗
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细胞死亡机制
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药物递送系统
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DOI
高影响因子
Discover Oncology
·
2024
·Vol. 15
·期 1
·1-18
·
IF 2.8
Feng Rui,Li Haolin,Meng Tong,Fei Mingtian,Yang Cheng
Purpose This study aimed to construct an m6A and cuproptosis-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using the information acquired from The Cancer Genome Atlas (TCGA) database. Methods First, the co-expression analysis was performed to identify lncRNAs linked with N6-methyladenosine (m6A) and cuproptosis in ccRCC. Then, a model encompassing four candidate lncRNAs was constructed via univariate, least absolute shrinkage together with selection operator (LASSO), and multivariate regression analyses. Furthermore, Kaplan–Meier, principal component, functional enrichment annotation, and nomogram analyses were performed to develop a risk model that could effectively assess medical outcomes for ccRCC cases. Moreover, the cellular function of NFE4 in Caki-1/OS-RC-2 cultures was elucidated through CCK-8/EdU assessments and Transwell experiments. Dataset outcomes indicated that NFE4 can have possible implications in m6A and cuproptosis, and may promote ccRCC progression. Results We constructed a panel of m6A and cuproptosis-related lncRNAs to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. Furthermore, the m6A and cuproptosis-related lncRNA model indicated higher diagnostic efficiency than other clinical features. Moreover, the NFE4 function analysis indicated a gene associated with m6A and cuproptosis-related lncRNAs in ccRCC. It was also revealed that the proliferation and migration of Caki-1 /OS-RC-2 cells were inhibited in the NFE4 knockdown group. Conclusion Overall, this study indicated that NFE4 and our constructed risk signature could predict outcomes and have potential clinical value.
研究领域:
生物信息学
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癌症生物学
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分子生物学
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基因组学
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DOI
PubMed
高影响因子
ACS Nano
·
2024
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IF 15.8
Shiyuan Hua,Huiqun Hu,Jin Liu,Feng Lu,Runchang Yu,Xuening Zhang,Haimeng Sun,Ziwei Wang,Yige Li,Jingyan Xia,Feng Xu,Min Zhou
Bacterial pneumonia is one of the most challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects. Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in the aerobic bacteria of the lungs. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, which can interact with copper and thus hinder the interaction of copper with proteins and assist in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large number of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions are further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug-delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid systemic toxicity that can be caused by large doses of copper.
研究领域:
药学
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纳米技术
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传染病学
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Chen Xiao,Xing Wang,Shiyou Li,Zhijie Zhang,Jiayuan Li,Qingyuan Deng,Xiang Chen,Xiangliang Yang,Zifu Li
Cuproptosis is a new kind of cell death that depends on delivering copper ions into mitochondria to trigger the aggradation of tricarboxylic acid (TCA) cycle proteins and has been observed in various cancer cells. However, whether cuproptosis occurs in cancer stem cells (CSCs) is unexplored thus far, and CSCs often reside in a hypoxic tumor microenvironment (TME) of triple negative breast cancers (TNBC), which suppresses the expression of the cuproptosis protein FDX1, thereby diminishing anticancer efficacy of cuproptosis. Herein, a ROS-responsive active targeting cuproptosis-based nanomedicine CuET@PHF is developed by stabilizing copper ionophores CuET nanocrystals with polydopamine and hydroxyethyl starch to eradicate CSCs. By taking advantage of the photothermal effects of CuET@PHF, tumor hypoxia is overcome via tumor mechanics normalization, thereby leading to enhanced cuproptosis and immunogenic cell death in 4T1 CSCs. As a result, the integration of CuET@PHF and mild photothermal therapy not only significantly suppresses tumor growth but also effectively inhibits tumor recurrence and distant metastasis by eliminating CSCs and augmenting antitumor immune responses. This study presents the first evidence of cuproptosis in CSCs, reveals that disrupting hypoxia augments cuproptosis cancer therapy, and establishes a paradigm for potent cancer therapy by simultaneously eliminating CSCs and boosting antitumor immunity.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2024
·
IF 5.8
Yicheng Jiang,Shuhan He,Niu Xiang,Linghui Duan,Yuxiang Lin,Wenyu Huang,Zhenghong Wu,Xiaole Qi
Definitely, copper homeostasis in mitochondria, and copper-triggered modality of mitochondrial cell death have been further confirmed. However, existing copper-based nanoplatforms were focused on synergistic therapies when the intracellular therapeutic targets were relatively scattered. Effective integrating of all targets within mitochondria to generate power coalescence remains a challenge. Herein, we develop a novel copper-based delivery system to trigger power coalescence and death vortex within tumor cell mitochondria. Specifically, a mitochondrial targeting "copper missile" loaded with curcumin (termed as Cur@CuS-TPP-HA, CCTH) was designed for cuproptosis/phototherapy/chemotherapy synergistic anti-tumor therapy. Once the CCTH NPs are shuttled to the mitochondria, near-infrared (NIR) irradiation initiates the release of copper ions and curcumin for in situ drug accumulation in cancer cell mitochondria. Excess of copper ions and curcumin can activate cuproptosis and mitochondrial apoptosis pathways respectively. When combined, they can cause an increase in reactive oxygen species (ROS), damage to mitochondrial DNA (mt-DNA), and a decrease in energy supply, thereby leading to a “vicious circle” of mitochondrial damage that further enhances tumor-killing efficacy. As a consequence, this "copper missile" exhibits advanced anti-tumor effects as verified through in vitro assessments and in vivo evaluations using the 4T1 breast tumor model, providing a promising approach for cuproptosis-based synergistic anti-tumor therapy.
研究领域:
肿瘤学
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药学
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Wang Yining,Zhou Qiaomei,Luo Wangping,Yang Xiaoyan,Zhang Jinguo,Lou Yijie,Mao Jin,Chen Jiayi,Wu Fan,Hou Jue,Tang Guping,Bai Hongzhen,Yu Risheng
Pancreatic ductal adenocarcinoma (PDAC), characterized by a dense extracellular matrix (ECM), presents significant therapeutic challenges due to its poor prognosis and high resistance to chemotherapy. Current chemodrugs and diagnostic agents largely fail to cross the barrier posed by the ECM, which severely limits the PDAC theranostics. This study introduces a novel theranostic strategy using thioether-hybridized hollow mesoporous organosilica nanoparticles (dsMNs) for the co-delivery of copper (Cu) and disulfiram (DSF), aiming to induce cuproptosis in PDAC cells. Our approach leverages the ECM-degrading enzyme collagenase, integrated with dsMNs, to enhance drug penetration by reducing matrix stiffness. Furthermore, the innovative use of a pancreatic cancer cell membrane coating on the nanoparticles enhances tumor targeting and stability (dsMCu-D@M-Co). The multifunctional platform not only facilitates deep drug penetration and triggers cuproptosis effectively but also utilizes the inherent properties of Cu to serve as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vitro and in vivo assessments demonstrate significant tumor size reduction in PDAC-bearing mice, highlighting the dual functionality of our platform in improving therapeutic efficacy and diagnostic precision. This integrated strategy represents a significant advancement in the management of PDAC, offering a promising new direction for overcoming one of the most lethal cancers.Graphical Abstract
研究领域:
肿瘤学
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纳米技术
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生物医学工程
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药学
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诊断影像学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
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IF 6.6
Wenjie Xie,Yixun Zhang,Qianfeng Xu,Guowei Zhong,Jundong Lin,Huichan He,Qiuling Du,Huijing Tan,Muqi Chen,Zhenjie Wu,Yulin Deng,Zhaodong Han,Jianming Lu,Jianheng Ye,Fen Zou,Yangjia Zhuo,Weide Zhong
Purpose Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa.Methods We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated.Results We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects.Conclusion The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment.
研究领域:
肿瘤学
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纳米技术
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药学
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材料科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）