Antimony Component Schottky Nanoheterojunctions as Ultrasound‐Heightened Pyroptosis Initiators for Sonocatalytic Immunotherapy

Pyroptosis, an inflammatory modality of programmed cell death associated with the immune response, can be initiated by bioactive ions and reactive oxygen species (ROS). However, bioactive ion-induced pyroptosis lacks specificity, and further exploration of other ions that can induce pyroptosis in cancer cells is needed. Sonocatalytic therapy (SCT) holds promise due to its exceptional penetration depth; however, the rapid recombination of electron-hole (e^--h⁺) pairs and the complex tumor microenvironment (TME) impede its broader application. Herein, we discovered that antimony (Sb)-based nanomaterials induced pyroptosis in cancer cells. Therefore, Schottky heterojunctions containing Sb component (Sb₂Se₃@Pt) were effectively designed and constructed via in situ growth of platinum (Pt) nanoparticles (NPs) on Sb₂Se₃ semiconductor with narrow band gaps, which were utilized as US-heightened pyroptosis initiators to induce highly effective pyroptosis in cancer cells to boost SCT-immunotherapy. Under US irradiation, excited electrons were transferred from Sb₂Se₃ nanorods (NRs) to the co-catalyst Pt via Schottky junctions, and band bending effectively prevented electron backflow and achieved efficient ROS generation. Moreover, the pores oxidized and depleted the overexpressed GSH in the TME, potentially amplifying ROS generation. The biological effects of the Sb₂Se₃@Pt nanoheterojunction itself combined with the sonocatalytic amplification of oxidative stress significantly induced Caspase-1/GSDMD-dependent pyroptosis in cancer cells. Therefore, SCT treatment with Sb₂Se₃@Pt not only effectively restrained tumor proliferation but also induced potent immune memory responses and suppressed tumor recurrence. Furthermore, the integration of this innovative strategy with immune checkpoint blockade (ICB) treatment elicited a systemic immune response, effectively augmenting therapeutic effects and impeding the growth of abscopal tumors. Overall, this study provides further opportunities to explore pyroptosis-mediated SCT-immunotherapy.