From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapies

Programmed cell death (PCD) plays a crucial role in preventing cancer initiation and progression. Among the diverse PCD pathways, cuproptosis, pyroptosis, and ferroptosis have garnered attention for their unique mechanisms, which not only directly eliminate tumor cells but also enhance anti-tumor im...

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Main Authors: Zhan Zhang, Yuanzhen Wu, Yanchen Liu, Jingyu Zhang, Yan Zhang, Yunlu Dai, Caigang Liu
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-10-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25002889
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author Zhan Zhang
Yuanzhen Wu
Yanchen Liu
Jingyu Zhang
Yan Zhang
Yunlu Dai
Caigang Liu
author_facet Zhan Zhang
Yuanzhen Wu
Yanchen Liu
Jingyu Zhang
Yan Zhang
Yunlu Dai
Caigang Liu
author_sort Zhan Zhang
collection DOAJ
description Programmed cell death (PCD) plays a crucial role in preventing cancer initiation and progression. Among the diverse PCD pathways, cuproptosis, pyroptosis, and ferroptosis have garnered attention for their unique mechanisms, which not only directly eliminate tumor cells but also enhance anti-tumor immunity. However, the therapeutic efficacy of PCD inducers is often compromised by rapid compensatory pathways in tumor cells, accelerated drug metabolism, and a lack of specificity, which can result in severe side effects. Engineered nanomedicines offer distinct advantages by leveraging nanoscale physicochemical properties to optimize pharmacokinetics, efficacy, and safety in cancer therapy. These nanomedicines enable precise targeting of tumor cells while enhancing drug stability. Moreover, they can simultaneously activate multiple PCD pathways and integrate with conventional therapies to further amplify anti-tumor effects. This review systematically examines the pathophysiological roles, mechanisms, and therapeutic implications of cuproptosis, pyroptosis, and ferroptosis in cancer treatment, with an emphasis on their modulation by nanomedicines. It also explores the potential interactions among these PCD pathways and highlights recent advancements in nanomedicine-based combination therapies targeting multiple PCD mechanisms. Finally, the challenges, limitations, and prospects for the clinical translation and application of PCD-targeting nanomedicines are discussed.
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institution Kabale University
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publisher KeAi Communications Co., Ltd.
record_format Article
series Bioactive Materials
spelling doaj-art-eefe48ba7cb545868cd6239e27b5c4772025-08-24T05:13:50ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-10-015277380910.1016/j.bioactmat.2025.06.052From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapiesZhan Zhang0Yuanzhen Wu1Yanchen Liu2Jingyu Zhang3Yan Zhang4Yunlu Dai5Caigang Liu6Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang, China; Corresponding author. Cancer Stem Cell and Translational Medicine Laboratory, Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 110000, Liaoning, China.Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, ChinaCancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China; MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau, SAR 999078, China; Corresponding author. Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau Macau, SAR 999078, China.Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang, China; Corresponding author. Cancer Stem Cell and Translational Medicine Laboratory, Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 110000, Liaoning, China.Programmed cell death (PCD) plays a crucial role in preventing cancer initiation and progression. Among the diverse PCD pathways, cuproptosis, pyroptosis, and ferroptosis have garnered attention for their unique mechanisms, which not only directly eliminate tumor cells but also enhance anti-tumor immunity. However, the therapeutic efficacy of PCD inducers is often compromised by rapid compensatory pathways in tumor cells, accelerated drug metabolism, and a lack of specificity, which can result in severe side effects. Engineered nanomedicines offer distinct advantages by leveraging nanoscale physicochemical properties to optimize pharmacokinetics, efficacy, and safety in cancer therapy. These nanomedicines enable precise targeting of tumor cells while enhancing drug stability. Moreover, they can simultaneously activate multiple PCD pathways and integrate with conventional therapies to further amplify anti-tumor effects. This review systematically examines the pathophysiological roles, mechanisms, and therapeutic implications of cuproptosis, pyroptosis, and ferroptosis in cancer treatment, with an emphasis on their modulation by nanomedicines. It also explores the potential interactions among these PCD pathways and highlights recent advancements in nanomedicine-based combination therapies targeting multiple PCD mechanisms. Finally, the challenges, limitations, and prospects for the clinical translation and application of PCD-targeting nanomedicines are discussed.http://www.sciencedirect.com/science/article/pii/S2452199X25002889Programmed cell deathBiomaterialNanomedicineCuproptosisPyroptosisFerroptosis
spellingShingle Zhan Zhang
Yuanzhen Wu
Yanchen Liu
Jingyu Zhang
Yan Zhang
Yunlu Dai
Caigang Liu
From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapies
Bioactive Materials
Programmed cell death
Biomaterial
Nanomedicine
Cuproptosis
Pyroptosis
Ferroptosis
title From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapies
title_full From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapies
title_fullStr From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapies
title_full_unstemmed From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapies
title_short From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapies
title_sort from mechanism to application programmed cell death pathways in nanomedicine driven cancer therapies
topic Programmed cell death
Biomaterial
Nanomedicine
Cuproptosis
Pyroptosis
Ferroptosis
url http://www.sciencedirect.com/science/article/pii/S2452199X25002889
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