Bioactive sonodynamic nanomaterials for immunogenic cell death programming and antitumor immune conversion

Sonodynamic therapy (SDT) has emerged as a noninvasive strategy for cancer nanomedicine because ultrasound can activate nanosonosensitizers deep within tissues and generate localized oxidative stress. However, the immunological value of SDT is still frequently inferred from tumor inhibition or immunogenic cell death (ICD)-associated markers alone. A central challenge is to determine how sonodynamic nanomaterials convert acoustic input into immune-decodable tumor-cell stress and systemic antitumor immunity. This Review summarizes how bioactive sonodynamic nanomaterials regulate ICD through three interconnected dimensions: stress intensity, molecular composition, and temporal coordination. We first discuss the physicochemical origins of SDT-induced ICD, including acoustic energy deposition, cavitation behavior, sensitizer activation routes, electronic-structure and interfacial charge-transfer engineering, redox productivity, tumor-microenvironmental gatekeeping, and organelle-focused oxidative injury. We then examine how regulated death programs, including pyroptosis, PANoptosis, ferroptosis, cuproptosis, and emerging execution modes, shape immune-decodable death rather than serving as isolated pathway labels. Particular attention is given to nanomaterial design strategies that control acoustic-redox conversion, subcellular stress routing, immune handover, checkpoint resistance, innate sensing, and tumor-microenvironment remodeling. Finally, we propose a benchmark-to-claim framework that aligns acoustic comparability, material definition, immune evidence depth, model realism, biosafety, manufacturability, and translational credibility with the strength of immune-related claims. SDT-based nanomedicine should be evaluated not only by ROS generation or local tumor ablation, but by whether nanomaterial-defined acoustic activation produces interpretable ICD, APC engagement, adaptive immune priming, and systemic functional consequence. This framework positions sonodynamic nanomaterials as programmable interfaces for antitumor immune conversion and provides a disciplined basis for future translational development.