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

Immunotherapy stands as a powerful weapon against tumors. However, tumor cells evade recognition and attack by the immune system through various mechanisms, achieving immune escape and exhibiting resistance to immunotherapy. Metalloimmunotherapy, as an emerging paradigm for immunotherapy, offers the...

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Main Authors: Cong Xia, Zirun Luo, Zhen Feng, Qianshi Zhang, Chenglai Xia
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1646890/full
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author Cong Xia
Zirun Luo
Zhen Feng
Qianshi Zhang
Chenglai Xia
author_facet Cong Xia
Zirun Luo
Zhen Feng
Qianshi Zhang
Chenglai Xia
author_sort Cong Xia
collection DOAJ
description Immunotherapy stands as a powerful weapon against tumors. However, tumor cells evade recognition and attack by the immune system through various mechanisms, achieving immune escape and exhibiting resistance to immunotherapy. Metalloimmunotherapy, as an emerging paradigm for immunotherapy, offers the potential to effectively overcome the limitations of current tumor immunotherapies. Nevertheless, developing highly efficient and specific metal-based agents for regulating the tumor immune system remains a significant challenge. The modulation of oxidative stress in the tumor microenvironment (TME) by metals presents novel breakthroughs for metalloimmunotherapy, particularly in enhancing immune responses, optimizing immune cell function, and reprogramming the immunosuppressive TME. Copper, a transition metal closely associated with tumor development, acts as an immune activator to enhance immune responses through oxidative stress. Benefiting from advances in nanomaterials, copper-based nanomedicines have demonstrated significant potential in improving the efficacy of cancer immunotherapy by modulating oxidative stress via Fenton-like reactions and enzymatic catalytic activities. Therefore, summarizing recent advances in copper-based nanomedicine activating tumor immunity through oxidative stress modulation provides new insights and drives progress for metalloimmunology. This review outlines strategies utilizing oxidative stress modulated by copper-based nanomedicines to induce or enhance immunotherapy through multiple forms of regulated cell death (RCD), drug co-delivery approaches, and versatile combination therapies. Finally, we discuss current challenges and offer perspectives on copper-based nanomedicines in tumor immunotherapy. Our review aims to elucidate the potential of copper-based nanomedicines in tumor immunology, providing insights for the future development of tumor immunotherapies based on metal and redox biology.
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spelling doaj-art-e905f0727efd4ddbbf31624e3d6421162025-08-20T03:17:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16468901646890Mechanism and application of copper-based nanomedicines in activating tumor immunity through oxidative stress modulationCong Xia0Zirun Luo1Zhen Feng2Qianshi Zhang3Chenglai Xia4Department of Gastrointestinal Surgery, The Second Hospital of Dalian Medical University, Dalian, ChinaDepartment of Breast, Thyroid and Head-Neck Surgery, The Third Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Gastrointestinal Surgery, The Second Hospital of Dalian Medical University, Dalian, ChinaDepartment of Gastrointestinal Surgery, The Second Hospital of Dalian Medical University, Dalian, ChinaScientific Research Center, Foshan Women and Children Hospital Affiliated with Guangdong Medical University, Foshan, ChinaImmunotherapy stands as a powerful weapon against tumors. However, tumor cells evade recognition and attack by the immune system through various mechanisms, achieving immune escape and exhibiting resistance to immunotherapy. Metalloimmunotherapy, as an emerging paradigm for immunotherapy, offers the potential to effectively overcome the limitations of current tumor immunotherapies. Nevertheless, developing highly efficient and specific metal-based agents for regulating the tumor immune system remains a significant challenge. The modulation of oxidative stress in the tumor microenvironment (TME) by metals presents novel breakthroughs for metalloimmunotherapy, particularly in enhancing immune responses, optimizing immune cell function, and reprogramming the immunosuppressive TME. Copper, a transition metal closely associated with tumor development, acts as an immune activator to enhance immune responses through oxidative stress. Benefiting from advances in nanomaterials, copper-based nanomedicines have demonstrated significant potential in improving the efficacy of cancer immunotherapy by modulating oxidative stress via Fenton-like reactions and enzymatic catalytic activities. Therefore, summarizing recent advances in copper-based nanomedicine activating tumor immunity through oxidative stress modulation provides new insights and drives progress for metalloimmunology. This review outlines strategies utilizing oxidative stress modulated by copper-based nanomedicines to induce or enhance immunotherapy through multiple forms of regulated cell death (RCD), drug co-delivery approaches, and versatile combination therapies. Finally, we discuss current challenges and offer perspectives on copper-based nanomedicines in tumor immunotherapy. Our review aims to elucidate the potential of copper-based nanomedicines in tumor immunology, providing insights for the future development of tumor immunotherapies based on metal and redox biology.https://www.frontiersin.org/articles/10.3389/fphar.2025.1646890/fullcoppernanomedicineoxidative stresstumor immunotherapyregulated cell death (RCD)
spellingShingle Cong Xia
Zirun Luo
Zhen Feng
Qianshi Zhang
Chenglai Xia
Mechanism and application of copper-based nanomedicines in activating tumor immunity through oxidative stress modulation
Frontiers in Pharmacology
copper
nanomedicine
oxidative stress
tumor immunotherapy
regulated cell death (RCD)
title Mechanism and application of copper-based nanomedicines in activating tumor immunity through oxidative stress modulation
title_full Mechanism and application of copper-based nanomedicines in activating tumor immunity through oxidative stress modulation
title_fullStr Mechanism and application of copper-based nanomedicines in activating tumor immunity through oxidative stress modulation
title_full_unstemmed Mechanism and application of copper-based nanomedicines in activating tumor immunity through oxidative stress modulation
title_short Mechanism and application of copper-based nanomedicines in activating tumor immunity through oxidative stress modulation
title_sort mechanism and application of copper based nanomedicines in activating tumor immunity through oxidative stress modulation
topic copper
nanomedicine
oxidative stress
tumor immunotherapy
regulated cell death (RCD)
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1646890/full
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