The rise of sono-immunotherapy in Glioblastoma therapy

A bstract GBM represents a paradigmatic challenge in oncology, characterized by a distinctively immunosuppressive tumor microenvironment and the formidable BBB that impedes conventional therapeutic delivery. While immunotherapy has revolutionized cancer treatment, its efficacy in GBM remains limited by the “immune-cold” nature of these tumors. Sono-immunotherapy has emerged as a transformative strategy, leveraging the deep-tissue penetration of FUS to mechanically and thermally modulate the TME. This review provides a comprehensive synthesis of the converging frontiers between acoustic physics, immunology, and advanced biomaterials science. We critically examine how ultrasound-responsive biomaterials—ranging from engineered sonosensitizers and functionalized nanocarriers to genetically modified bacteria—orchestrate potent antitumor immunity. We detail the mechanisms by which these bioactive agents harness ultrasonic energy to induce ICD, breach the BBB/brain-tumor barrier, and repolarize tumor-associated macrophages. Furthermore, we highlight recent innovations in “sono-activatable” engineered living materials, such as bacteria programmed with thermal switches for precise payload release. By integrating materials engineering with immuno-oncology, this review outlines a roadmap for next-generation sono-immunotherapeutic platforms capable of overcoming the systemic and local barriers in GBM treatment.