Nanoplatforms-Enhanced High-Intensity Focused Ultrasound for Cancer Immunotherapy

High-intensity focused ultrasound (HIFU) is a non-invasive tumor therapy capable of activating anti-tumor immunity through the induction of immunogenic cell death. However, its therapeutic efficacy is constrained by several limitations, including energy attenuation, incomplete ablation, and the exacerbation of the immunosuppressive tumor microenvironment. Recently, a variety of nanoplatforms have been engineered as potent enhancers for HIFU, primarily including perfluorocarbons, metal-organic frameworks, and polymer-based nanomaterials. These nanoplatforms synergistically enhance both the physical destruction and immune activation efficacy of HIFU through mechanisms such as intensifying cavitation or thermal effects, functioning as smart drug depots for responsive drug release, or acting as nanomotors to facilitate deep tissue penetration. This review systematically summarizes the latest strategies and synergistic mechanisms by which these nanoplatforms augment HIFU-based immunotherapy, with a focus on comparing their differences in HIFU-enhancing mechanisms, immunomodulatory methods, and major anti-tumor outcomes. Furthermore, we critically analyze their respective advantages and limitations, and discuss the current challenges and future directions.