Shin Weon Sup, Park Soon Ki, Verwilst Peter, Koo Seyoung, Lee Joung Hae, Chi Sung-Gil, Kim Jong Seung
Department of Chemistry, Korea University, Seoul 02841, Korea.
Department of Life Sciences, Korea University, Seoul 02841, Korea.
Chem Commun (Camb). 2017 Jan 19;53(7):1281-1284. doi: 10.1039/c6cc08977a.
We report on a mitochondria-specific combinational theranostic agent, 1. This system contains a chlorambucil prodrug and an aggregation induced emission dye. In addition, compound 1 bears both an intracellular thiol-triggered moiety and a mitochondria targeting unit (triphenylphosphonium). Glutathione (GSH) is the most abundant thiol and its concentrations are significantly higher in a great number of cancer cell lines, compared to normal cells. The GSH-induced prodrug 1 upon activation releases chlorambucil and exhibits mitochondria targeted aggregation induced emission (AIE) fluorescence, resulting in cell apoptosis via the caspase pathway due to mitochondrial dysfunction.
我们报道了一种线粒体特异性联合诊疗剂，即化合物1。该体系包含苯丁酸氮芥前药和一种聚集诱导发光染料。此外，化合物1兼具细胞内硫醇触发部分和线粒体靶向单元（三苯基鏻）。谷胱甘肽（GSH）是最丰富的硫醇，与正常细胞相比，其在大量癌细胞系中的浓度显著更高。激活后，GSH诱导的前药1释放出苯丁酸氮芥，并表现出线粒体靶向的聚集诱导发光（AIE）荧光，由于线粒体功能障碍，通过半胱天冬酶途径导致细胞凋亡。
