Department of Chemistry, Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
J Am Chem Soc. 2023 Aug 16;145(32):17689-17699. doi: 10.1021/jacs.3c04027. Epub 2023 Aug 7.
Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect and apoptosis resistance often limit their therapeutic efficacy. Herein, we demonstrated for the first time that linking luminogens with aggregation-induced emission effect (AIEgens) into COF networks via vinyl linkages was an effective strategy to construct nonmetallic pyroptosis inducers for boosting antitumor immunity. Mechanistic investigations revealed that the formation of the vinyl linkage in the AIE COF endowed it with not only high brightness but also strong light absorption ability, long lifetime, and high quantum yield to favor the generation of reactive oxygen species for eliciting pyroptosis. In addition, the synergized system of the AIE COF and αPD-1 not only effectively eradicated primary and distant tumors but also inhibited tumor recurrence and metastasis in a bilateral 4T1 tumor model.
共价有机框架（COFs）因其独特的特性，如光吸收、生物相容性和光稳定性，已成为一类很有前途的用于癌症光疗的结晶多孔材料。然而，聚集引起的猝灭效应和细胞凋亡抗性常常限制了它们的治疗效果。在此，我们首次证明，通过乙烯基键将发光体与具有聚集诱导发光效应（AIEgens）的化合物连接到 COF 网络中，是构建非金属细胞焦亡诱导剂以增强抗肿瘤免疫的有效策略。机理研究表明，AIE COF 中乙烯基键的形成不仅赋予其高亮度，而且还赋予其强的光吸收能力、长的寿命和高的量子产率，有利于产生活性氧以引发细胞焦亡。此外，AIE COF 和 αPD-1 的协同系统不仅能有效地消除原发和远处肿瘤，而且还能抑制双侧 4T1 肿瘤模型中的肿瘤复发和转移。
