Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
National Key Laboratory of Green Pesticide, College of Chemistry, Central China Normal University, Wuhan, 430079, China.
Nat Commun. 2024 Sep 18;15(1):8187. doi: 10.1038/s41467-024-52458-4.
Cancer is a significant cause of death around the world, and for many varieties, treatment is not successful. Therefore, there is a need for the development of innovative, efficacious, and precisely targeted treatments. Here, we develop a series of Au(I) complexes (1-4) through rational manipulation of ligand structures, thereby achieving tumor cell specific targeting and orchestrated tumor eradication via chemo-phototherapy and induced immunogenic cell death. A comprehensive exploration based on in vitro and in vivo female mice experimentation shows that complex 4 exhibits proficiency in specific tumor imaging, endoplasmic reticulum targeting, and has robust therapeutic capabilities. Mechanistic elucidation indicates that the anticancer effect derives from the synergistic actions of thioredoxin reductase inhibition, highly efficient reactive oxygen species production and immunogenic cell death. This work presents a report on a robust Au(I) complex integrating three therapeutic modalities within a singular system. The strategy presented in this work provides a valuable reference for the development of high-performance therapeutic agents.
癌症是全球范围内主要的致死原因之一，对于许多癌症类型，目前的治疗方法并不成功。因此，我们需要开发创新的、有效的、精准靶向的治疗方法。在这里，我们通过合理设计配体结构，开发了一系列的 Au(I) 配合物（1-4），从而通过化疗-光疗和诱导免疫原性细胞死亡来实现肿瘤细胞的特异性靶向和协同肿瘤清除。基于体外和体内雌性小鼠实验的全面探索表明，配合物 4 具有优异的特异性肿瘤成像、内质网靶向和强大的治疗能力。机制研究表明，抗癌作用源自于硫氧还蛋白还原酶抑制、高效活性氧产生和免疫原性细胞死亡的协同作用。本工作报道了一种强大的 Au(I) 配合物，它将三种治疗模式集成在一个单一的体系中。本工作中提出的策略为开发高性能治疗剂提供了有价值的参考。
