化学
前药
活性氧
谷胱甘肽
下调和上调
细胞凋亡
癌症研究
生物物理学
药理学
生物化学
酶
医学
生物
基因
作者
Jianqiang Qian,Zhongyuan Xu,Chunyan Meng,Yun Liu,Hongmei Wu,Yunyun Wang,Jing Yang,Hao Zheng,Fansheng Ran,Gong‐Qing Liu,Yong Ling
标识
DOI:10.1021/acs.jmedchem.2c00130
摘要
A novel theranostic co-prodrug SCB has been designed by combining a co-prodrug from CDDO-Me and SAHA with a biotin-coupled near-infrared (NIR) probe hemicyanine via redox-responsive linker thiolactate to enhance the tumor theranostic efficacy and reduce the toxic side effects using both active and passive targeting strategies. SCB displayed reactive oxygen species (ROS)- and glutathione (GSH)-dependent release of NIR fluorescence and two parent drugs. Furthermore, the administration of SCB caused selective illumination of the tumor tissues for >24 h, thereby guiding precise removal of a tumor from intraoperative mice. Importantly, SCB exhibited highly efficient tumor inhibition, exerted selective combination therapy through prodrug mode, and minimized the adverse effects. Finally, SCB induced mitochondrial depolarization, DNA damage, and cell apoptosis through ROS generation and downregulation of HDAC6 protein, as verified by H2AX, Bax, cleaved-PARP, and Mcl-1 proteins. Thus, we suggest that SCB can provide a new platform for both precise diagnosis-guided tumor removal and selective combination therapy with high safety.
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