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用于协同铜死亡免疫治疗的工程化抗癌纳米药物

Engineered anti-cancer nanomedicine for synergistic cuproptosis-immunotherapy.

作者信息

Li Jiaxin, Pang Xinlong, Xin Zhongwei, Song Liang, Liu Xiangyan, Zhang Xinyu, Yang Zhe

机构信息

Tumor Research and Therapy Center, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong, Jinan, 250022, China.

Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, Shandong, Jinan, 250022, China.

出版信息

Mater Today Bio. 2025 Jul 29;34:102133. doi: 10.1016/j.mtbio.2025.102133. eCollection 2025 Oct.


DOI:10.1016/j.mtbio.2025.102133
PMID:40791799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12336686/
Abstract

Tumor immunotherapy has seen remarkable progress in recent cancer treatments. However, its broad clinical application is hindered by several challenges, such as the low immunogenicity of "cold tumors," immunosuppressive conditions within the tumor microenvironment, and persistent immune evasion of cancer cells. Therefore, selectively enhancing the immune response during cancer therapy is crucial. Cuproptosis is a newly identified form of regulated cell death that is characterized by the accumulation of intracellular copper ions, leading to lipoylated protein aggregation and subsequent metabolic dysfunction. This process is intricately linked with the tumor microenvironment. By activating targeted mechanisms, cuproptosis can selectively trigger immune responses within tumor regions, thereby addressing the issue of tumor-mediated immune evasion. Cuproptosis holds promise for improving the efficacy of immunotherapy by promoting a more robust anti-tumor immune response within the tumor microenvironment. The combination of cuproptosis-inducing strategies with immunotherapeutic approaches presents a novel and potentially effective direction for future cancer treatment.

摘要

肿瘤免疫疗法在近期的癌症治疗中取得了显著进展。然而,它在临床上的广泛应用受到了几个挑战的阻碍,例如“冷肿瘤”的低免疫原性、肿瘤微环境中的免疫抑制状态以及癌细胞持续的免疫逃逸。因此,在癌症治疗过程中选择性地增强免疫反应至关重要。铜死亡是一种新发现的程序性细胞死亡形式,其特征是细胞内铜离子积累,导致脂酰化蛋白聚集以及随后的代谢功能障碍。这个过程与肿瘤微环境有着复杂的联系。通过激活靶向机制,铜死亡可以在肿瘤区域选择性地触发免疫反应,从而解决肿瘤介导的免疫逃逸问题。铜死亡有望通过在肿瘤微环境中促进更强有力的抗肿瘤免疫反应来提高免疫治疗的疗效。诱导铜死亡的策略与免疫治疗方法的结合为未来癌症治疗提供了一个新颖且可能有效的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/e5ccd159cf7a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/c3c1cb58e1a2/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/09200380d21f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/e1e8631ab323/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/f6f255a66d6c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/e1741fc7bd64/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/17416f423b8a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/138b464e1431/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/e5ccd159cf7a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/c3c1cb58e1a2/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/09200380d21f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/e1e8631ab323/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/f6f255a66d6c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/e1741fc7bd64/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/17416f423b8a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/138b464e1431/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1079/12336686/e5ccd159cf7a/gr7.jpg

相似文献

[1]
Engineered anti-cancer nanomedicine for synergistic cuproptosis-immunotherapy.

Mater Today Bio. 2025-7-29

[2]
A tumor microenvironment-responsive nanocomposite for enhanced copper retention and hypoxia reversal to promote cuproptosis in tumor treatment.

Acta Biomater. 2025-7-4

[3]
Cuproptosis: a novel therapeutic mechanism in lung cancer.

Cancer Cell Int. 2025-6-24

[4]
Interplay between tumor mutation burden and the tumor microenvironment predicts the prognosis of pan-cancer anti-PD-1/PD-L1 therapy.

Front Immunol. 2025-7-24

[5]
A Self-Amplifying MOF Nanoplatform for Cancer Immunotherapy Synergizing Starvation-Enhanced Cuproptosis and cGAS-STING Activation.

ACS Appl Mater Interfaces. 2025-7-16

[6]
Nanoparticles induced cuproptosis to enhance antitumor immunotherapy.

J Nanobiotechnology. 2025-7-28

[7]
Oncolytic reovirus enhances the effect of CEA immunotherapy when combined with PD1-PDL1 inhibitor in a colorectal cancer model.

Immunotherapy. 2025-4

[8]
Cuproptosis: mechanisms and nanotherapeutic strategies in cancer and beyond.

Chem Soc Rev. 2025-6-30

[9]
Cuproptosis: A Review on Mechanisms, Role in Solid and Hematological Tumors, and Association with Viral Infections.

Mediterr J Hematol Infect Dis. 2025-7-1

[10]
A biomimetic cuproptosis amplifier for targeted NIR-II fluorescence/photoacoustic imaging-guided synergistic NIR-II photothermal immunotherapy.

Biomaterials. 2024-3

本文引用的文献

[1]
Development of a novel Cu-Mn hydroxide layered nanosheet-loaded drug modulating the tumour microenvironment and enhancing antitumor effects.

J Colloid Interface Sci. 2025-10-15

[2]
Ultrasound-Triggered Nanoparticles Induce Cuproptosis for Enhancing Immunogenic Sonodynamic Therapy.

Adv Mater. 2025-7

[3]
The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer.

Signal Transduct Target Ther. 2025-5-9

[4]
A new formula for calculating normal tissue complication probability.

Precis Radiat Oncol. 2024-9-19

[5]
Enhanced Electroacoustic Tomography with Supervised Learning for Real-time Electroporation Monitoring.

Precis Radiat Oncol. 2024-9-22

[6]
Radiotherapy promotes cuproptosis and synergizes with cuproptosis inducers to overcome tumor radioresistance.

Cancer Cell. 2025-6-9

[7]
One-Step Symbiosis of Bimetallic Peroxides Nanoparticles to Induce Ferroptosis/Cuproptosis and Activate cGAS-STING Pathway for Enhanced Tumor Immunotherapy.

Adv Mater. 2025-5

[8]
Deciphering the value of anoikis-related genes in prognosis, immune microenvironment, and drug sensitivity of laryngeal squamous cell carcinoma.

Pathol Res Pract. 2025-4

[9]
Reshaping the immune microenvironment and reversing immunosenescence by natural products: Prospects for immunotherapy in gastric cancer.

Semin Cancer Biol. 2025-5

[10]
Bimetallic nanoreactor mediates cascade amplification of oxidative stress for complementary chemodynamic-immunotherapy of tumor.

Biomaterials. 2025-6

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