Near-Infrared Light-Responsive Immunomodulator Prodrugs Rejuvenating Immune Microenvironment for “Cold” Tumor Photoimmunotherapy
Jiaping Shen1,2, Bin Xu1,2, Yun Zheng3, Xingyu Zhao1,2, Huixuan Qi1,2, Yongan Tang3, Wenhai Lin1,2（林文孩）*, Shengliang Li3（李盛亮）*, Zhiyuan Zhong1,2,3（钟志远）*
1Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China
2State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China
3College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
Angew. Chem. Int. Ed. 2025, 64, e202425309
Abstract: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.
Article information: //doi.org/10.1002/anie.202425309
