Cui Cen, Yuliang Yang, Yijian Gao, Jie Yu, Haoyu Wang, Xiandie Qian, Yujie Ma, Huan Chen, Hai Huang, Zihan Su, Lijun Kan, Xiliang Li, Yujun Zhang, Shengliang Li
Pancreatic cancer is a highly immunosuppressive “cold” tumor that typically fails to achieve satisfactory immunotherapy outcomes. Photoimmunotherapy represents a preeminent cancer treatment strategy that combines the advantages of noninvasive phototherapy and drug-free immunotherapy. However, recently reported phototherapeutic materials predominantly respond to visible light via the oxygen-dependent pathway, severely weakening their efficacy in hypoxic and deep-seated tumors. Herein, a dimerization strategy for a near-infrared II (NIR-II)-emissive luminophore is developed for efficient image-guided photoimmunotherapy of “cold” pancreatic tumors. Owing to their dimeric design, the nanoparticles (NPs) of the dimeric luminophore ( d- NBT) exhibited improved absorption and NIR-II fluorescence emission, along with efficient type-I reactive oxygen species (ROS) generation and sufficient photothermal conversion performance under 808 nm light irradiation. With NIR-II imaging, d- NBT NPs have been demonstrated to provide high-resolution whole-body angiography beyond 1500 nm and efficient tumor accumulation. The complete ablation of pancreatic tumors in primary and KPC tumor models were achieved via the photoimmunotherapy effect of d- NBT NPs. This study provides a dimerization strategy for high-performance NIR-II emissive luminophores for imaging-guided photoimmunotherapy of “cold” pancreatic cancer.