Zhao Zhennan, Gao Pan, You Yuanyuan, Chen Tianfeng
Department of Chemistry, Jinan University, Guangzhou, 510632, P.R. China.
Chemistry. 2018 Mar 2;24(13):3289-3298. doi: 10.1002/chem.201705561. Epub 2018 Feb 5.
A mutifunctional ruthenium-based conjugate Ru-BSe was designed and synthesized. The Ru complex with favorable bioimaging function was covalently linked with a cancer-targeted molecule that could be effectively internalized by the tumor to realize enhanced theranostic effects. The pH-response of the Ru conjugate in tumor acidic microenvironment causes ligand substitution and release of therapeutic complex. This activated complex remains inert to the reducing biomolecule-glutathione and terminally locates in mitochondria, in which it triggers oxidative stress, and activates intrinsic apoptosis. Real-time monitoring reveals that this Ru conjugate could selectively accumulate in tumor tissue in vivo, which significantly suppresses tumor progression and alleviate the damage to normal organs, realizing the precise cancer theranosis.
设计并合成了一种多功能钌基共轭物Ru-BSe。具有良好生物成像功能的钌配合物与一种可被肿瘤有效内化的癌症靶向分子共价连接，以实现增强的治疗诊断效果。钌共轭物在肿瘤酸性微环境中的pH响应会导致配体置换和治疗性配合物的释放。这种活化的配合物对还原性生物分子谷胱甘肽保持惰性，并最终定位于线粒体，在其中引发氧化应激并激活内源性凋亡。实时监测表明，这种钌共轭物能够在体内选择性地积聚在肿瘤组织中，显著抑制肿瘤进展并减轻对正常器官的损伤，实现精确的癌症治疗诊断。
