Molecular Engineering of NIR‐II/IIb Emitting AIEgen for Multimodal Imaging‐Guided Photo‐Immunotherapy

In view of the great challenges related to the complexity and heterogeneity of tumors, efficient combination therapy is an ideal strategy for eliminating primary tumors and inhibiting distant tumors. A novel aggregation‐induced emission (AIE) phototherapeutic agent called T‐TBBTD is developed, which features a donor–acceptor–donor (D–A–D) structure, enhanced twisted molecule conformation, and prolonged second near‐infrared window (NIR‐II) emission. The multimodal imaging function of the molecule has significance for its treatment time window and excellent photothermal/photodynamic performance for multimode therapy. The precise molecular structure and versatility provide prospects for molecular therapy for anti‐tumor applications. Fluorescence imaging in the NIR‐II window offers advantages with enhanced spatial resolution, temporal resolution, and penetration depth. The prepared AIE@R837 NPs also have controllable performance for antitumor photo‐immunotherapy. Following local photo‐irradiation, AIE@R837 NPs generate abundant heat, and 1O2 directly kills tumor cells, induces immunogenic cell death (ICD) as a photo‐therapeutic effect, and releases R837, which enhances the synergistic effect of antigen presentation and contributes to the long‐lasting protective antitumor immunity. A bilateral 4T1 tumor model revealed that this photo‐immunotherapy can eliminate primary tumors. More importantly, it has a significant inhibitory effect on distant tumor growth. Therefore, this method can provide a new strategy for tumor therapy. This work reports a novel donor–acceptor–donor structured AIE agent T‐TBBTD featuring excellent NIR‐II emission properties for in vivo multimodal imaging, excellent PTT/PDT performance, and robust photostability under 808‐nm laser irradiation.