Nanoparticles induced cuproptosis to enhance antitumor immunotherapy

Abstract Immunotherapy is a highly promising cancer treatment method. However, it is limited by low immunogenicity and an immunosuppressive microenvironment, which could be relieved by immunogenic cell death (ICD). Currently, effective ICD is primarily achieved through apoptosis induction, but tumor...

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Main Authors: Wen Deng, Zichen Zhong, Haojie Shang, Yonghua Tong, Qiu Huang, Yu He, Jian Wu, Xiaozhuo Ba, Zhiqiang Chen, Yuan Chen, Kun Tang
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03616-3
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author Wen Deng
Zichen Zhong
Haojie Shang
Yonghua Tong
Qiu Huang
Yu He
Jian Wu
Xiaozhuo Ba
Zhiqiang Chen
Yuan Chen
Kun Tang
author_facet Wen Deng
Zichen Zhong
Haojie Shang
Yonghua Tong
Qiu Huang
Yu He
Jian Wu
Xiaozhuo Ba
Zhiqiang Chen
Yuan Chen
Kun Tang
author_sort Wen Deng
collection DOAJ
description Abstract Immunotherapy is a highly promising cancer treatment method. However, it is limited by low immunogenicity and an immunosuppressive microenvironment, which could be relieved by immunogenic cell death (ICD). Currently, effective ICD is primarily achieved through apoptosis induction, but tumor cells' resistance to apoptosis limits its antitumor efficacy. Therefore, developing new cell death modalities with high immunogenicity for cancer immunotherapy is of great significance. Cuproptosis, a newly discovered form of programmed cell death, can effectively circumvent tumor cells' resistance to apoptosis. Various Cu ionophores have been studied as anticancer drugs to promote cuproptosis, but the lack of tumor specificity remains one of the major challenges in this field. In contrast, nanoparticles tend to preferentially accumulate in tumor tissues due to the enhanced permeability and retention (EPR) effect, and they can be surface-modified to achieve active tumor targeting capabilities. Recently, many unique physicochemical properties of nanoparticles have been designed as nano-inducers of cuproptosis, successfully enhancing immunotherapy. Based on this, this review detailedly summarized various strategies and applications of nanoparticles-induced cuproptosis in tumor cells. The role of Cu metabolism and homeostasis in tumorigenesis and development, the molecular mechanisms of cuproptosis and different cuproptosis inducers with promising application prospects, as well as the interaction between cuproptosis and immunotherapy have also been reviewed. Finally, we presented the limitations and future prospects of cuproptosis nano-inducers, hoping to provide a new strategy to enhance antitumor immunotherapy. Graphical Abstract
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spelling doaj-art-2cb40c3d5ce044dea2bb0e177f59a6ce2025-08-20T04:02:55ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123114110.1186/s12951-025-03616-3Nanoparticles induced cuproptosis to enhance antitumor immunotherapyWen Deng0Zichen Zhong1Haojie Shang2Yonghua Tong3Qiu Huang4Yu He5Jian Wu6Xiaozhuo Ba7Zhiqiang Chen8Yuan Chen9Kun Tang10Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Immunotherapy is a highly promising cancer treatment method. However, it is limited by low immunogenicity and an immunosuppressive microenvironment, which could be relieved by immunogenic cell death (ICD). Currently, effective ICD is primarily achieved through apoptosis induction, but tumor cells' resistance to apoptosis limits its antitumor efficacy. Therefore, developing new cell death modalities with high immunogenicity for cancer immunotherapy is of great significance. Cuproptosis, a newly discovered form of programmed cell death, can effectively circumvent tumor cells' resistance to apoptosis. Various Cu ionophores have been studied as anticancer drugs to promote cuproptosis, but the lack of tumor specificity remains one of the major challenges in this field. In contrast, nanoparticles tend to preferentially accumulate in tumor tissues due to the enhanced permeability and retention (EPR) effect, and they can be surface-modified to achieve active tumor targeting capabilities. Recently, many unique physicochemical properties of nanoparticles have been designed as nano-inducers of cuproptosis, successfully enhancing immunotherapy. Based on this, this review detailedly summarized various strategies and applications of nanoparticles-induced cuproptosis in tumor cells. The role of Cu metabolism and homeostasis in tumorigenesis and development, the molecular mechanisms of cuproptosis and different cuproptosis inducers with promising application prospects, as well as the interaction between cuproptosis and immunotherapy have also been reviewed. Finally, we presented the limitations and future prospects of cuproptosis nano-inducers, hoping to provide a new strategy to enhance antitumor immunotherapy. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03616-3NanoparticlesCuproptosisImmunogenic cell deathCancer immunotherapy
spellingShingle Wen Deng
Zichen Zhong
Haojie Shang
Yonghua Tong
Qiu Huang
Yu He
Jian Wu
Xiaozhuo Ba
Zhiqiang Chen
Yuan Chen
Kun Tang
Nanoparticles induced cuproptosis to enhance antitumor immunotherapy
Journal of Nanobiotechnology
Nanoparticles
Cuproptosis
Immunogenic cell death
Cancer immunotherapy
title Nanoparticles induced cuproptosis to enhance antitumor immunotherapy
title_full Nanoparticles induced cuproptosis to enhance antitumor immunotherapy
title_fullStr Nanoparticles induced cuproptosis to enhance antitumor immunotherapy
title_full_unstemmed Nanoparticles induced cuproptosis to enhance antitumor immunotherapy
title_short Nanoparticles induced cuproptosis to enhance antitumor immunotherapy
title_sort nanoparticles induced cuproptosis to enhance antitumor immunotherapy
topic Nanoparticles
Cuproptosis
Immunogenic cell death
Cancer immunotherapy
url https://doi.org/10.1186/s12951-025-03616-3
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