Reprogramming tumor immune microenvironment by ultrasound‐responsive nanoplatforms for enhanced cancer immunotherapy

Abstract Cancer immunotherapy represents a significant advancement in cancer treatment by enhancing the specific recognition and elimination of cancer cells. However, its efficacy is substantially hindered by the immunosuppressive nature of the tumor immune microenvironment (TIME). Recently, ultrasound (US)‐responsive nanoplatforms have emerged as a promising strategy to precisely reprogram the TIME by leveraging unique ultrasonic properties for spatiotemporal regulation of the activities of tumor cells, immune cells, and non‐immune stromal cells. This review summarizes the recent progress in engineering US‐responsive nanoplatforms aimed at reprogramming various critical cell populations of TIME. We first discuss US‐responsive nanoplatform strategies that target key organelles in tumor cells, including mitochondria, lysosomes, endoplasmic reticulum, and nucleus, to induce immunogenic cell death and enhance therapeutic efficacy. We also present US‐responsive nanoplatforms that regulate immune cells, including T cells, dendritic cells, macrophages, and natural killer cells, to reprogram the TIME. Additionally, we highlight how US‐responsive nanoplatforms can target non‐immune stromal cells, such as cancer‐associated fibroblasts and tumor endothelial cells, to inhibit angiogenesis and reverse immunosuppressive barriers. Finally, we discuss challenges in clinical translation and provide insights for future directions of US‐responsive nanoplatforms to reprogram the TIME for enhanced cancer immunotherapy.