Metal Complexes Stimulating Immunogenic Pyroptosis as Burgeoning Antitumor Strategy

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.