Targeting CDK1 and copper homeostasis in breast cancer via a nanopolymer drug delivery system.

IF 5.3 2区 医学 Q2 CELL BIOLOGY Cell Biology and Toxicology Pub Date : 2024-12-26 DOI:10.1007/s10565-024-09958-2
Nan Shang, Lisi Zhu, Yan Li, Chengyang Song, Xiaodan Liu
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Abstract

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.

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通过纳米聚合物给药系统靶向CDK1和铜在乳腺癌中的稳态。
乳腺癌(BRCA)的患病率在女性人群中是显著的,作为一种常见的恶性肿瘤,其中铜水平的管理是治疗成功的关键。本研究旨在探讨铜稳态对BRCA治疗的影响,特别关注周期蛋白依赖性激酶1 (Cyclin-Dependent Kinase 1, CDK1)的作用及其与铜调控的关系。一种含有纳米颗粒(NPs)的新型热敏水凝胶与化疗药物长春新碱(VCR)协同抑制肿瘤生长和转移。通过包括生物信息学分析、体外实验和体内模型在内的综合方法,该研究确定CDK1是铜稳态下BRCA进展的重要因素。MBVP-Gel是一种新型的含有NPs的热敏水凝胶,用于增强化疗药物的递送和调节乳腺癌治疗中的铜稳态。MBVP-Gel由铜螯合物和VCR NPs组成,可有效抑制CDK1表达,从而抑制BRCA细胞的生长和转移,同时增强VCR的治疗效果。该研究为铜稳态与BRCA之间的相互作用提供了新的见解和实验验证,为完善未来的治疗策略提供了有价值的基础。这些发现强调了靶向铜稳态和CDK1在加强BRCA治疗方面的潜在优势,为个体化干预奠定了基础,并改善了患者的预后。
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阿拉丁
Triton X-100
来源期刊
Cell Biology and Toxicology
Cell Biology and Toxicology 生物-毒理学
CiteScore
9.90
自引率
4.90%
发文量
101
审稿时长
>12 weeks
期刊介绍: Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.
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