International Journal of Nanomedicine
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2025
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IF 6.5
Manjia Zheng,Ziwei Chen,Jiling Xie,Qiyuan Yang,Minhua Mo,Liangjiao Chen
Background: The cerebral cortex is the foundation of cognitive function, and an imbalance in copper homeostasis in the cerebral cortex may cause cognitive and memory dysfunction. Metal exposure may disrupt copper (Cu) homeostasis in cells, leading to cognitive impairment. Yttrium oxide nanoparticles (Y2O3 NPs) are widely used in the biomedical field and have potential neurotoxicity. However, the influence of Y2O3 NPs on cognitive memory function in the brain is currently unclear.Methods: The effects of Y2O3 NPs on cognitive and memory function were evaluated by rat behavioural experiments after intraperitoneal injection in a rat model. Subsequently, histological analysis was conducted on the cerebral cortex, and the Cu content and expression levels of cuproptosis-related proteins were detected both in vitro and in vivo. Finally, the copper output protein Cu transporting alpha polypeptide (ATP7A) was screened and detected at the mRNA and protein levels. Plasmid transfection experiments further confirmed that Y2O3 NPs mediate disordered Cu output through ATP7A.Results: Y2O3 NP exposure induced cognitive and memory dysfunction in rats. This effect was related to the disruption of copper homeostasis in neuronal cells caused by Y2O3 NPs, which induced cuproptosis. Further research revealed that Y2O3 NPs downregulate ATP7A expression, thus disrupting copper output and inducing cuproptosis.Conclusion: Y2O3 NPs induce cognitive and memory dysfunction by mediating the disruption of copper output in neuronal cells, revealing the toxicity of Y2O3 NPs to neurons. These findings contribute to their safe application in the biomedical field.
研究领域:
神经科学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
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IF 14.7
Guan Meng,Cheng Kai,Xie Xiao-Ting,Li Yong,Ma Meng-Wen,Zhang Bin,Chen Si,Chen Wei,Liu Bo,Fan Jin-Xuan,Zhao Yuan-Di
Cuproptosis is an emerging mode of programmed cell death for tumor suppression but sometimes gets resisted by tumor cells resist under specific mechanisms. Inhibiting copper transporter ATPase (ATP7A) was found to disrupt copper ion homeostasis, thereby enhancing the effect of cuproptosis and eventually inhibiting tumor invasion and metastasis. In this study, we develop a multifunctional nanoplatfrom based on Cu 9 S 8 (CAPSH), designed to enhance cuproptosis in tumor cells by specifically targeting ATP7A interference, while combining thermodynamic therapy with immune effects. The release of copper ions from CAPSH and the copper homeostasis interference by siRNA cooperatively increases the concentration of copper ions in tumor cells, which induces effectively cuproptosis and activates immune responses for suppressing development and metastasis of tumor. This nanoplatform simultaneously regulates cuproptosis from both principles of onset and development, facilitating the application of cuproptosis in tumor therapy.
研究领域:
肿瘤学
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分子生物学
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纳米技术
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免疫学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2025
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IF 6
Guofeng Wang,Shiwei Xu,Chao Deng,Yueyue Feng,Liying Huang,Qin Guo,Yajun Wang,Min Zhang,Qian Shi,Nannan Liu
Copper ions (Cu + and Cu 2+ ) are vital for physiological functions, and their imbalance is implicated in disease progression. However, simultaneous detection of both species is challenging due to their similar properties. Here, we report a dual-functionalized glass micropipette sensor enabling independent detection of Cu + and Cu 2+ . UiO-66-NH 2 was grown in situ on the inner wall to capture Cu 2+ via amino coordination, reducing ionic current. Glutathione-functionalized carbon nanotubes (GCNTs) coated on the outer surface bind Cu + , increasing SERS signal via enhanced surface defects. The sensor exhibits a wide detection range (10 -1 –10 5 μM), a detection limit of 0.1 μM, and allows simultaneous monitoring of Cu + /Cu 2+ in the physiological range (2–10 μM). It further distinguishes copper ion levels in MCF-10A and MCF-7 cells, revealing altered copper homeostasis in cancer. This platform offers a sensitive, selective tool for studying copper in biological systems.
研究领域:
生物化学
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分析化学
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医学
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DOI
PubMed
高影响因子
CELL BIOLOGY AND TOXICOLOGY
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2024
·Vol. 41
·期 1
·1-29
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IF 5.3
Shang Nan,Zhu Lisi,Li Yan,Song Chengyang,Liu Xiaodan
The prevalence of breast cancer (BRCA) is notable in the female population, being a commonly diagnosed malignancy, where the management of copper levels is crucial for treatment success. This research aims to explore the influence of copper homeostasis on BRCA therapy, with a specific focus on the role of Cyclin-Dependent Kinase 1 (CDK1) and its relationship to copper regulation. A novel thermosensitive hydrogel incorporating nanoparticles (NPs) was engineered to synergize with the chemotherapy drug vincristine (VCR) in inhibiting tumor growth and metastasis. Through a comprehensive approach involving bioinformatics analyses, in vitro experiments, and in vivo models, the study identified CDK1 as a significant factor in BRCA progression under copper homeostasis. MBVP-Gel, a novel thermosensitive hydrogel incorporating NPs, was developed to enhance the delivery of chemotherapy drugs and regulate copper homeostasis in breast cancer treatment. The MBVP-Gel, formulated with copper chelation and VCR NPs, effectively suppressed CDK1 expression, thereby restraining BRCA cell growth and metastasis while enhancing the therapeutic impact of VCR. This investigation offers fresh insights and experimental validation on the interaction between copper homeostasis and BRCA, providing a valuable foundation for refining future treatment strategies. These findings underscore the potential advantages of targeting copper homeostasis and CDK1 in enhancing BRCA therapy, setting the stage for individualized interventions and improved patient consequences.
研究领域:
肿瘤学
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药理学
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纳米技术
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癌症生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Shiwen Wang,Ying Shen,Binbin Hu,Qiping Wu,Nanzhou Wang,Zichao Wang,Zifeng Zhang,Yujie Li,Jianhui Jiang
Breast cancer therapy confronts dual challenges of metabolic plasticity-driven drug resistance and immunosuppression. To address this, we developed DCP-TPP, a therapeutic nanoplatform that integrates dysregulation of copper homeostasis and lipid metabolism for precise breast cancer therapy. Leveraging the overexpression of cluster of differentiation 36 (CD36) in breast cancer cells, DCP-TPP employs fatty acid camouflage (PCM) to deliver disulfiram (DSF) and photothermal Cu3BiS3 to cancer cells and features triphenylphosphonium (TPP) modification for targeted mitochondrial drug delivery. Near-infrared (NIR) irradiation triggers the phase transition of DCP-TPP’s outer layer, inducing spatiotemporal release of DSF to liberate copper ions from inert Cu3BiS3, thereby generating diethyldithiocarbamate–copper complex (CuET). This disrupts copper homeostasis and induces cuproptosis, which subsequently triggers S-acetyltransferase (DLAT) aggregation, impairing tricarboxylic acid (TCA) cycle flux, acetyl-CoA production, ATP citrate lyase (Acly)-dependent lipogenesis, and ultimately collapses mitochondrial oxidative phosphorylation. Multiomics profiling revealed oleic acid depletion, arachidonic acid oxidation, and glutathione exhaustion, collectively amplifying metabolic collapse. DCP-TPP-induced cell death enhanced dendritic cell (DC) activation and CD8+ T cell infiltration. In breast cancer models, DCP-TPP achieved 90.9% tumor suppression, with 60% of mice resisting rechallenge. By transforming lipid metabolic dependency into a therapeutic vulnerability and coupling it with copper ion toxicity, DCP-TPP offers a promising strategy for breast cancer therapy.
研究领域:
癌症生物学
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纳米医学
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免疫治疗
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代谢工程
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生物无机化学
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靶向药物递送
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DOI
PubMed
高影响因子
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