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Metal Complexes Stimulating Immunogenic Pyroptosis as Burgeoning Antitumor Strategy
Yue Zheng1,2, Kun Peng1,3, Qian Cao1
1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti-Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat-Sen University, Guangzhou, 510006, China.
Abstract:
The exploration of antitumor agents with diverse action mechanisms has become an important focus in both fundamental research and clinical oncology, driven by the need for more effective cancer therapies. Metal complexes, with their versatile chemical, photophysical, and biological properties, represent an ideal class of therapeutic and diagnostic candidates for investigating novel antitumor mechanisms. Recent advances have underscored their unique ability to trigger diverse cell death pathways. Among these, pyroptosis, an inflammatory form of programmed cell death, has garnered substantial attention because of its intrinsic link to antitumor immunity. This minireview focuses on the cutting-edge developments in antitumor metal complexes designed to induce pyroptosis and elucidates their pyroptosis-stimulating mechanisms across chemo-, photo-, sono- and targeted therapeutic modalities. By dissecting the interplay among pyroptosis induction, biological processes, such as inflammasome activation and gasdermin cleavage, and subsequent immune reprogramming, we provide a thorough overview of the action mechanisms of metal complex-based pyroptosis inducers. This understanding has inspired the rational development of novel anticancer metal complexes that can remodel the tumor microenvironment and synergize with immunotherapies.
Insights
Metal complexes are being developed as novel anticancer agents that trigger pyroptosis, an inflammatory cell death pathway. These agents offer new strategies for cancer therapy by stimulating antitumor immunity and reprogramming the tumor microenvironment.
Area of Science:
- Materials Science
- Oncology
- Immunology
Background:
- The need for novel antitumor agents with diverse mechanisms is critical in cancer research and clinical oncology.
- Metal complexes offer unique properties for developing therapeutic and diagnostic cancer agents.
- Pyroptosis, an inflammatory programmed cell death, is gaining attention for its role in antitumor immunity.
Purpose of the Study:
- To review recent advancements in antitumor metal complexes designed to induce pyroptosis.
- To elucidate the mechanisms by which these metal complexes stimulate pyroptosis.
- To explore the potential of metal complex-based pyroptosis inducers in cancer therapy and immunotherapy.
Main Methods:
- Review of current literature on metal complexes and pyroptosis induction.
- Analysis of pyroptosis-stimulating mechanisms across various therapeutic modalities (chemo-, photo-, sono-, targeted therapy).
- Dissection of the interplay between pyroptosis, inflammasome activation, gasdermin cleavage, and immune reprogramming.
Main Results:
- Metal complexes can effectively induce pyroptosis through diverse therapeutic approaches.
- Understanding the molecular mechanisms of pyroptosis induction by metal complexes is crucial.
- These complexes can reprogram the tumor microenvironment and enhance antitumor immunity.
Conclusions:
- Antitumor metal complexes that induce pyroptosis represent a promising strategy for cancer treatment.
- These agents can synergize with immunotherapies by modulating the tumor immune response.
- Further development of metal complex-based pyroptosis inducers holds potential for innovative cancer therapies.
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