Activating Immunogenic Cell Death and Reprogramming the Tumor Microenvironment to Enhance Radiotherapy for Breast Cancer via Low-Frequency Ultrasound-Driven “Artificial T Cells”

The immunosuppressive tumor microenvironment (TME) is a key factor that reduces the effectiveness of radiotherapy in breast cancer, as it limits the ability of cytotoxic T lymphocytes (CTLs) to effectively target and eliminate tumor cells. In this study, T cell membrane components were incorporated and granzyme B (GrB) was loaded to construct biomimetic microbubbles with a core-shell structure (GrB@TMBs), named "artificial T cells". Low-frequency ultrasound (LFUS) mediates the "cavitation effect" of GrB@TMBs, causing the formation of micropores on the tumor cell membrane and releasing GrB cross these pores, thereby mimicking the process of CTLs killing tumor cells. Consequently, up to 1.99-fold of dendritic cells and 2.87-fold of tumor-specific T cells in the TME were observed with the US + GrB@TMBs group compared to the free GrB group. Furthermore, the use of LFUS-driven "artificial T cells" to enhance breast cancer radiotherapy led to the elimination of 40% of tumors, prolonged survival, and the promotion of long-term immune memory formation. In summary, LFUS-driven "artificial T cells" provide a promising strategy for improving the efficacy of breast cancer radiotherapy.