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基于金属有机框架的肿瘤靶向纳米材料通过促进肝癌细胞中的铜死亡和焦亡来介导肿瘤免疫治疗。

Tumor-targeting nanomaterials based on metal-organic frameworks mediate tumor immunotherapy by promoting cuproptosis and pyroptosis in hepatocellular carcinoma cells.

作者信息

Yi Xiaoyuan, Xie Huaying, Huang Kunzhao, Luo Jianzhang, Li Wen, Zeng Qingyu, He Feifei, Shi Wuxiang, Wang Duo, Wang Liyan

机构信息

Digestive Department, The Affiliated Hospital of Guilin Medical University, Lequn road No.15, Xiufeng district, Guilin, 541001, China.

Health Management Unit, Faculty of Humanities and Management, Guilin Medical University, Guilin, Guangxi, 541199, China.

出版信息

Mater Today Bio. 2025 Apr 8;32:101745. doi: 10.1016/j.mtbio.2025.101745. eCollection 2025 Jun.


DOI:10.1016/j.mtbio.2025.101745
PMID:40275951
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12019074/
Abstract

Activating a robust immune response is an effective strategy for achieving tumor eradication. In this study, copper-based metal-organic framework nanoparticles (referred to as FA-PZ@MOF NPs), which have the ability to simultaneously induce cuproptosis and pyroptosis in tumor cells, were designed to utilize the synergistic effects of cuproptosis and pyroptosis to trigger immunogenic cell death (ICD). This can inhibit tumor growth, migration, and metastasis while enabling efficient antitumor immunotherapy. The nano inducer targets hepatocellular carcinoma tumor cells via folic acid, dissociates and releases copper ions in the tumor microenvironment (TME), which has a high glutathione concentration, leading to copper ion overload, thereby mediating cuproptosis. Additionally, the released ZnO generates substantial amounts of HO and Zn in the acidic environment, enhancing the Cu-based Fenton-like reaction for chemokinetic therapy. This exacerbates the reactive oxygen species (ROS) storms and mitochondrial damage, and combined with the action of Polyphyllin VI (PPVI), induces pyroptosis and cuproptosis. This multilayered interaction strategy also triggers robust ICD while inhibiting hepatocellular carcinoma tumor metastasis and invasion.

摘要

激活强大的免疫反应是实现肿瘤根除的有效策略。在本研究中,设计了一种铜基金属有机框架纳米颗粒(称为FA-PZ@MOF NPs),其能够同时诱导肿瘤细胞发生铜死亡和焦亡,旨在利用铜死亡和焦亡的协同效应触发免疫原性细胞死亡(ICD)。这可以抑制肿瘤生长、迁移和转移,同时实现高效的抗肿瘤免疫治疗。这种纳米诱导剂通过叶酸靶向肝癌肿瘤细胞,在具有高谷胱甘肽浓度的肿瘤微环境(TME)中解离并释放铜离子,导致铜离子过载,从而介导铜死亡。此外,释放的ZnO在酸性环境中产生大量的羟基自由基和锌离子,增强基于铜的类芬顿反应用于化学动力学治疗。这加剧了活性氧(ROS)风暴和线粒体损伤,并与重楼皂苷VI(PPVI)的作用相结合,诱导焦亡和铜死亡。这种多层相互作用策略在抑制肝癌肿瘤转移和侵袭的同时,还能触发强大的ICD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/ad2fcef988ec/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/e17609f435a8/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/7bdb9825bf92/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/9aa289ec4bd1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/5a1830818080/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/e25044e39ee0/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/601a9d72eb1b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/ad2fcef988ec/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/e17609f435a8/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/7bdb9825bf92/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/9aa289ec4bd1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/5a1830818080/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/e25044e39ee0/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/601a9d72eb1b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84a/12019074/ad2fcef988ec/gr5.jpg

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[1]
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引用本文的文献

[1]
Mechanism and application of copper-based nanomedicines in activating tumor immunity through oxidative stress modulation.

Front Pharmacol. 2025-7-11

[2]
Cuproptosis: a novel therapeutic mechanism in lung cancer.

Cancer Cell Int. 2025-6-24

本文引用的文献

[1]
High Immunogenic Cuproptosis Evoked by In Situ Sulfidation-Activated Pyroptosis for Tumor-Targeted Immunotherapy of Colorectal Cancer.

Small Sci. 2024-1-17

[2]
Copper depletion-induced tumor cuproptosis.

Chem Sci. 2024-11-18

[3]
Orchestrated copper-loaded nanoreactor for simultaneous induction of cuproptosis and immunotherapeutic intervention in colorectal cancer.

Mater Today Bio. 2024-11-9

[4]
Dual-Synergistic Nanomodulator Alleviates Exosomal PD-L1 Expression Enabling Exhausted Cytotoxic T Lymphocytes Rejuvenation for Potentiated iRFA-Treated Hepatocellular Carcinoma Immunotherapy.

ACS Nano. 2024-11-26

[5]
Hollow Calcium/Copper Bimetallic Amplifier for Cuproptosis/Paraptosis/Apoptosis Cancer Therapy via Cascade Reinforcement of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction.

ACS Nano. 2024-10-29

[6]
Multi-Enzyme Nanoparticles as Efficient Pyroptosis and Immunogenic Cell Death Inducers for Cancer Immunotherapy.

Adv Sci (Weinh). 2024-11

[7]
Reprogramming the Tumor Immune Microenvironment Through Activatable Photothermal Therapy and GSH depletion Using Liposomal Gold Nanocages to Potentiate Anti-Metastatic Immunotherapy.

Small. 2024-12

[8]
A cuproptosis nanocapsule for cancer radiotherapy.

Nat Nanotechnol. 2024-12

[9]
Multifunctional Copper-Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy.

Adv Mater. 2024-11

[10]
Tumor microenvironment-responsive manganese-based nano-modulator activate the cGAS-STING pathway to enhance innate immune system response.

J Nanobiotechnology. 2024-9-3

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