State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
Small. 2023 Aug;19(32):e2300859. doi: 10.1002/smll.202300859. Epub 2023 Apr 17.
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 O 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.
鉴于肿瘤的复杂性和异质性带来的巨大挑战，高效的联合治疗是消除原发性肿瘤和抑制远处肿瘤的理想策略。本文开发了一种新型聚集诱导发射（AIE）光疗剂 T-TBBTD，其具有给体-受体-给体（D-A-D）结构、增强的扭曲分子构象和延长的近红外二区（NIR-II）发射。该分子的多模态成像功能对其治疗时间窗口具有重要意义，同时具有优异的光热/光动力性能，可实现多模式治疗。精确的分子结构和多功能性为抗肿瘤的分子治疗应用提供了前景。近红外二区的荧光成像具有增强的空间分辨率、时间分辨率和穿透深度的优势。所制备的 AIE@R837 NPs 还具有用于抗肿瘤光免疫治疗的可控性能。在局部光照射后，AIE@R837 NPs 产生丰富的热量，直接杀死肿瘤细胞，作为光疗效果诱导免疫原性细胞死亡（ICD），并释放 R837，增强抗原呈递的协同效应，有助于持久的抗肿瘤免疫保护。双侧 4T1 肿瘤模型表明，这种光免疫疗法可以消除原发性肿瘤。更重要的是，它对远处肿瘤的生长具有显著的抑制作用。因此，该方法可为肿瘤治疗提供新策略。
