NIR-II emissive nanomedicine of dimer-structured conjugated oligomer induces immunogenic cell death for photoimmunotherapy of pancreatic cancer

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.