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Mitochondria-Targeting Metallodrugs for Cancer Therapy: Perspectives from Cell Death Modes
Hao-Ming Li1, Meng-Meng Wang1,2, Yan Su1,3
1Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, P. R. China.
Abstract:
Mitochondria, recognized as the cellular powerhouses, are indispensable organelles responsible for crucial cellular processes, such as energy metabolism, material synthesis, and signaling transduction. Their intricate involvement in a broad spectrum of diseases, particularly cancer, has propelled the exploration of mitochondria-targeting treatment as a promising strategy for cancer therapy. Since the groundbreaking discovery of cisplatin, the trajectory of research on the development of metal complexes have been marked by continuous advancement, giving rise to a diverse array of metallodrugs characterized by variations in ligand types, metal center properties, and oxidation states. By specifically targeting mitochondria, these metallodrugs exhibit the remarkable ability to elicit various programmed cell death pathways, encompassing apoptosis, autophagy, and ferroptosis. This review primarily focuses on recent developments in transition metal-based mitochondria-targeting agents, offering a comprehensive exploration of their capacity to induce distinct cell death modes. The aim is not only to disseminate knowledge but also to stimulate an active field of research toward new clinical applications and novel anticancer mechanisms.
Insights
Mitochondria-targeting metallodrugs offer a promising cancer therapy strategy by inducing programmed cell death. This review explores recent advances in transition metal agents for novel anticancer mechanisms and clinical applications.
Area of Science:
- Biochemistry and Molecular Biology
- Oncology
- Medicinal Chemistry
Background:
- Mitochondria are vital organelles involved in cellular processes and implicated in various diseases, especially cancer.
- Targeting mitochondria presents a promising therapeutic strategy for cancer treatment.
- Metallodrug development has advanced significantly, yielding diverse metal complexes for therapeutic exploration.
Purpose of the Study:
- To review recent developments in transition metal-based mitochondria-targeting agents.
- To explore the capacity of these agents to induce distinct programmed cell death pathways (apoptosis, autophagy, ferroptosis).
- To stimulate research towards new clinical applications and anticancer mechanisms.
Main Methods:
- Literature review of recent advancements in mitochondria-targeting metallodrugs.
- Analysis of transition metal complexes with varying ligand types, metal centers, and oxidation states.
- Examination of studies detailing the induction of specific cell death modalities.
Main Results:
- Transition metal-based agents can be designed to specifically target mitochondria.
- These agents effectively induce various programmed cell death pathways, including apoptosis, autophagy, and ferroptosis.
- Diverse metallodrugs show potential for selective cancer cell killing.
Conclusions:
- Mitochondria-targeting metallodrugs represent a significant advancement in cancer therapy research.
- Induction of distinct cell death pathways by these agents offers novel therapeutic avenues.
- Further research is warranted to translate these findings into clinical applications.
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