Pyroptosis-Inducing Nanomedicine for Cancer Immunotherapy: Mechanisms and Emerging Strategies.

Cancer immunotherapy has revolutionized oncologic treatment, yet its efficacy remains constrained by tumor immune evasion and the immunosuppressive tumor microenvironment. Addressing these multifaceted barriers calls for strategies that can both eliminate cancer cells and simultaneously amplify antitumor immunity. Pyroptosis, a lytic and highly immunogenic form of programmed cell death mediated by gasdermin proteins, has recently emerged as a compelling approach to reprogram the tumor immune landscape. By releasing abundant damage-associated molecular patterns and pro-inflammatory cytokines, pyroptosis not only destroys tumor cells but also promotes antigen presentation and robust local-to-systemic immune responses. With the rapid advancement of nanotechnology, pyroptosis-engineered nanomedicine has gained increasing interest for synergizing cell killing and immune activation to enhance cancer immunotherapy. This review summarizes recent progress in the molecular mechanisms of pyroptosis and highlights emerging nanomedicine strategies designed to precisely induce pyroptosis within tumors. The discussion further extends to design principles, activation modalities, and therapeutic outcomes in preclinical models. Finally, current challenges and future directions toward clinical translation are outlined. Collectively, this review integrates pyroptosis biology with nanoengineering concepts to inspire next-generation immunotherapeutic interventions against cancer.