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Published on: January 11, 2019
From mechanism to application: programmed cell death pathways in nanomedicine-driven cancer therapies
Zhan Zhang1,2,3, Yuanzhen Wu1, Yanchen Liu1
1Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
Abstract:
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.
Insights
Engineered nanomedicines enhance programmed cell death (PCD) pathways like cuproptosis, pyroptosis, and ferroptosis for cancer therapy. These nanomedicines improve drug delivery and target multiple PCD mechanisms, overcoming treatment limitations.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Nanotechnology
Background:
- Programmed cell death (PCD) is vital in cancer prevention and progression.
- Cuproptosis, pyroptosis, and ferroptosis are key PCD pathways with direct anti-tumor effects and immune-boosting capabilities.
- Current PCD inducers face challenges like drug resistance, rapid metabolism, and off-target toxicity.
Purpose of the Study:
- To review the roles and mechanisms of cuproptosis, pyroptosis, and ferroptosis in cancer.
- To explore how nanomedicines can modulate these PCD pathways for enhanced cancer therapy.
- To discuss nanomedicine-based combination strategies targeting multiple PCD mechanisms.
Main Methods:
- Systematic review of existing literature on PCD pathways and nanomedicine applications in cancer.
- Analysis of the pathophysiological roles, mechanisms, and therapeutic implications of cuproptosis, pyroptosis, and ferroptosis.
- Examination of nanomedicine strategies for targeting and activating PCD pathways.
Main Results:
- Nanomedicines offer improved pharmacokinetics, targeted delivery, and enhanced stability for PCD inducers.
- Engineered nanomedicines can simultaneously activate multiple PCD pathways and combine with conventional therapies.
- Nanomedicine-based approaches show potential for overcoming limitations of single-pathway PCD induction.
Conclusions:
- Nanomedicines hold significant promise for optimizing cuproptosis, pyroptosis, and ferroptosis-based cancer therapies.
- Targeting multiple PCD pathways with nanomedicines can amplify anti-tumor effects and improve safety.
- Further research and clinical translation are needed to realize the full potential of PCD-targeting nanomedicines.
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