Configuration‐Mediated Efficient Non‐Radiative Transition for R848‐Assisted Photothermal Immunotherapy to Inhibit Tumor Growth and Metastasis by An <i>In Situ</i> Tumor Vaccine Strategy

Cancer metastasis remains a critical factor contributing to the current limitations in cancer treatment. Photothermal immunotherapy has emerged as a safe and potent therapeutic approach, demonstrating the capability to suppress tumor growth and metastasis. While researchers have extensively investigated various structural modifications to enhance photothermal conversion performance, the influence of molecular configuration has received comparatively limited attention. In this study, we synthesized two isomers, CZTBT and LVTBT, which possessed distinct configurations. LVTBT, characterized by a flatter molecular configuration, exhibited an extended absorption wavelength and a higher molar extinction coefficient. Its excited state facilitated stronger rotation for non-radiative transitions, leading to a high photothermal conversion efficiency (PCE) of 36.3 %. When combined with R848, LVTBT@R848 nanoparticles (NPs)-mediated photothermal immunotherapy functioned as an in situ tumor vaccine, promoting the maturation of dendritic cells (DCs), T cell infiltration, and the differentiation of natural killer (NK) cells and memory T cells, thereby activating the strong immune response. Consequently, it significantly inhibited the growth of both primary and distant tumors, while also limiting lung metastasis. In summary, this study proposed a configuration-mediated non-radiative transition strategy for efficient photothermal immunotherapy, advancing the frontiers of organic photothermal agents (OPTAs) design and synthesis.