Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

Cancer immunotherapy has the potential to revolutionize the treatment of malignant tumors, but its effectiveness is limited by the low immune response rate and immune-related adverse events. Pyroptosis, as an inflammatory programmed cell death type, triggers strong acute inflammatory response and antitumor immunity, converting "cold" tumors to "hot". Particularly, biomaterials loading pyroptosis inducers targeting the tumor microenvironment to engineer pyroptosis, have achieved great progress in recent years. Herein, the design strategy, mechanism pathway, and role of biomaterials to induce pyroptosis in cancer immunotherapy are comprehensively reviewed. The present review focuses on the application of biomaterials-induced pyroptosis in cancer immunotherapy, including nanogel, polymer prodrug, nanovesicle, and mesoporous material. Additionally, the synthesis of a series of stimuli-responsive nanoplatforms, including glutathione-responsive, pH-responsive, reactive oxygen species-responsive, and enzyme-mimicking catalytic performance, is described. Meanwhile, it augments multiple immune response processes of cell uptake, antigen presentation, T-cell activation, and expansion. Finally, the perspectives of pyroptosis-mediated inflammation to break through the tumor vascular basement membrane barrier achieving efficient volcanic penetration of biomaterials are discussed. Artificial intelligence, multi-omics analysis, and anthropogenic animal models of organoids are presented, aiming to provide guidance and assistance for constructing effective and controllable pyroptosis-engineered biomaterials and improving tumor immunotherapy. Cancer immunotherapy has the potential to revolutionize the treatment of malignancies, but its effectiveness is limited by low immune response rates. Tailored biomaterials precisely elicit pyroptosis, which is the plausible way to fuel a strong antitumor immune response. In this review, the design strategies, and mechanisms of biomaterial to induce pyroptosis and significance in tumor immunotherapy are discussed.image