Volume 64, Issue 27 e202507186
Minireview

Metal Complexes Stimulating Immunogenic Pyroptosis as Burgeoning Antitumor Strategy

Dr. Yue Zheng

Dr. Yue Zheng

MOE 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

Guangdong Province Key Laboratory of Pharmaceutical Bioactive Substances, School of Bioscience and Biopharmaceutics Guangdong Pharmaceutical University, Guangzhou, 510006 China

Both the authors contributed equally to this work.

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Dr. Kun Peng

Dr. Kun Peng

MOE 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

AIE Institute South China University of Technology, Guangzhou, 510640 China

Both the authors contributed equally to this work.

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Prof. Dr. Qian Cao

Corresponding Author

Prof. Dr. Qian Cao

MOE 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

E-mail: [email protected]; [email protected]

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Prof. Dr. Zong-Wan Mao

Corresponding Author

Prof. Dr. Zong-Wan Mao

MOE 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

State Key Laboratory of Coordination Chemistry Nanjing University, Nanjing, 210023 China

E-mail: [email protected]; [email protected]

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First published: 27 May 2025

Graphical Abstract

This minireview focuses on the cutting-edge developments in antitumor metal complexes designed to induce pyroptosis, elucidating their pyroptosis-stimulating mechanisms across chemo-, photo-, sono- and targeted therapeutic modalities, and proposes the prevailing challenges and future opportunities in metal-based immunotherapy.

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.

Conflict of Interests

The authors declare no conflict of interest.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this minireview.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.