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用于基于铜死亡的协同癌症治疗的靶向性氧化锌@铜-乙二胺纳米平台

Targeted ZnO@CuEA Nanoplatform for Cuproptosis-Based Synergistic Cancer Therapy.

作者信息

Zhang Hao, Liu Guoyan

机构信息

Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

出版信息

J Cell Mol Med. 2025 Jun;29(11):e70636. doi: 10.1111/jcmm.70636.


DOI:10.1111/jcmm.70636
PMID:40454964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12128471/
Abstract

Gastric cancer is a common malignant tumour. Copper-induced cell death, a recently discovered form of metal ion-related cell death, has garnered significant attention from researchers. We synthesised a multifunctional nanoparticle, ZnO@CuEA, and characterised its morphology using transmission electron microscopy. Cytotoxicity was analysed via CCK8 assays and calcein-AM staining. The tumour-targeting capability of ZnO@CuEA was validated using confocal microscopy and in vivo imaging experiments. RNA-seq and proteomic analysis were conducted to assess changes in mRNA and protein expression before and after ZnO@CuEA treatment. Lysosomal β-galactosidase staining was employed for cellular senescence detection, and protein expression levels were analysed via Western blot. Finally, in vivo experiments demonstrated the tumour-inhibitory effect of ZnO@CuEA. ZnO@CuEA is a multifunctional nanoparticle capable of targeting tumour cells and inducing cuproptosis. In vivo experiments showed that ZnO@CuEA exhibits significant antitumor activity. The multifunctional nanoparticles synthesised in this study provide a novel therapeutic approach for cancer treatment.

摘要

胃癌是一种常见的恶性肿瘤。铜诱导的细胞死亡是一种最近发现的与金属离子相关的细胞死亡形式,已引起研究人员的广泛关注。我们合成了一种多功能纳米颗粒ZnO@CuEA,并使用透射电子显微镜对其形态进行了表征。通过CCK8测定法和钙黄绿素-AM染色分析细胞毒性。使用共聚焦显微镜和体内成像实验验证了ZnO@CuEA的肿瘤靶向能力。进行RNA测序和蛋白质组分析以评估ZnO@CuEA处理前后mRNA和蛋白质表达的变化。采用溶酶体β-半乳糖苷酶染色进行细胞衰老检测,并通过蛋白质印迹分析蛋白质表达水平。最后,体内实验证明了ZnO@CuEA的肿瘤抑制作用。ZnO@CuEA是一种能够靶向肿瘤细胞并诱导铜死亡的多功能纳米颗粒。体内实验表明,ZnO@CuEA具有显著的抗肿瘤活性。本研究中合成的多功能纳米颗粒为癌症治疗提供了一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/a7bfaef58a10/JCMM-29-e70636-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/1b68e0fd20db/JCMM-29-e70636-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/299b71a4bff1/JCMM-29-e70636-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/c409486dc6b6/JCMM-29-e70636-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/3feacbfaed49/JCMM-29-e70636-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/0f6f03abc334/JCMM-29-e70636-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/86949e5c0845/JCMM-29-e70636-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/a7bfaef58a10/JCMM-29-e70636-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/1b68e0fd20db/JCMM-29-e70636-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/299b71a4bff1/JCMM-29-e70636-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/c409486dc6b6/JCMM-29-e70636-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/3feacbfaed49/JCMM-29-e70636-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/0f6f03abc334/JCMM-29-e70636-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/86949e5c0845/JCMM-29-e70636-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2eb/12128471/a7bfaef58a10/JCMM-29-e70636-g006.jpg

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[1]
Targeted ZnO@CuEA Nanoplatform for Cuproptosis-Based Synergistic Cancer Therapy.

J Cell Mol Med. 2025-6

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[6]
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[8]
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本文引用的文献

[1]
Spermidine alleviates copper-induced oxidative stress, inflammation and cuproptosis in the liver.

FASEB J. 2025-3-31

[2]
NIR-Actuated Ferroptosis Nanomotor for Enhanced Tumor Penetration and Therapy.

Adv Mater. 2024-12

[3]
A cuproptosis nanocapsule for cancer radiotherapy.

Nat Nanotechnol. 2024-12

[4]
Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives.

J Hematol Oncol. 2024-8-16

[5]
Glutathione-Scavenging Celastrol-Cu Nanoparticles Induce Self-Amplified Cuproptosis for Augmented Cancer Immunotherapy.

Adv Mater. 2024-8

[6]
"Triple-Punch" Strategy Exosome-Mimetic Nanovesicles for Triple Negative Breast Cancer Therapy.

ACS Nano. 2024-2-9

[7]
Cuproptosis: Harnessing Transition Metal for Cancer Therapy.

ACS Nano. 2023-10-24

[8]
AuPt-Loaded Cu-Doped Polydopamine Nanocomposites with Multienzyme-Mimic Activities for Dual-Modal Imaging-Guided and Cuproptosis-Enhanced Photothermal/Nanocatalytic Therapy.

Anal Chem. 2023-9-19

[9]
The advancing of polymeric core-shell ZnO nanocomposites containing 5-fluorouracil for improving anticancer activity in colorectal cancer.

Naunyn Schmiedebergs Arch Pharmacol. 2024-2

[10]
Functional Nucleic Acids-Engineered Bio-Barcode Nanoplatforms for Targeted Synergistic Therapy of Multidrug-Resistant Cancer.

ACS Nano. 2023-7-25

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