Sonodynamic Molecules for Tumor Immunotherapy and Immunoimaging

Abstract

Sonodynamic therapy (SDT) has emerged as a promising cancer treatment modality owing to its noninvasive nature and deep tissue penetration capability. Beyond direct tumor ablation, SDT can modulate antitumor immunity, which drives the development of high-performance sonodynamic platforms for precise and potent immunoregulation. In this review, we summarize recent advances in molecular engineering strategies for developing intelligent sonosensitizers capable of orchestrating diverse immunological processes. These advanced platforms promote robust immunogenic cell death through enhanced reactive oxygen species generation, amplify immune activation by mimicking costimulatory signaling or integrating genetically engineered bacteria, enable ultrasound-triggered and in situ release of immune checkpoint inhibitors through responsive linkers, and potentiate STING signaling via responsive prodrug designs, thereby coordinating innate and adaptive immune responses. In addition, activatable acoustic afterglow probes have been developed for real-time visualization of immune-cell activity, tumor immune microenvironment dynamics, and SDT-induced immunogenic events, providing valuable feedback on therapeutic efficacy. Collectively, this review highlights the molecular design principles, functional mechanisms, and biomedical applications of engineered sonodynamic systems, guiding the development of next-generation platforms for precision cancer immunotherapy and immune imaging.