Near‐Infrared Light‐Responsive Immunomodulator Prodrugs Rejuvenating Immune Microenvironment for “Cold” Tumor Photoimmunotherapy

Light-activatable prodrugs have been applied in precision cancer therapy because of their spatiotemporal controllability and minimal toxic side effects. However, the reported prodrugs were limited by the ultraviolet and visible light regions, which seriously restricted their application in deep tissues. Developing a near-infrared (NIR) light-activatable release system remains a great challenge. Herein, the 808 nm light-activatable prodrugs were constructed with imiquimod (R837) and NIR boron dipyrromethene (BODIPY) via a reactive oxygen species (ROS)-cleavable linker for photoimmunotherapy of "cold" cancer. ROS produced by BODIPY could cleave the linker under 808 nm laser irradiation, and R837 was released spatiotemporally at the tumor site. The combination of the immune response produced by R837 and immunogenic cell death caused by phototherapy significantly potentiated adaptive antitumor immunity and enhanced cytotoxic CD8⁺ T cell infiltration for tumor metastasis and distant tumor inhibition. This work provides an effective NIR light-activatable controlled release system for cancer immunotherapy and metastasis suppression.