College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University , Jinan 250014, People's Republic of China.
Anal Chem. 2016 Jun 21;88(12):6450-6. doi: 10.1021/acs.analchem.6b01135. Epub 2016 Jun 3.
To reduce the side effects of chemotherapy, nontoxic prodrugs activated by the tumor microenvironment are urgently required for use in cancer treatment. In this work, we developed prodrug 4 for tumor-targeting treatment and imaging of the anticancer drug release in vivo. Taking advantage of the high glutathione (GSH) concentration in cancer cells, the disulfide bond in prodrug 4 was cleaved, resulting in the release of an active anticancer drug and a near-infrared (NIR) fluorescence dye turn-on. Furthermore, contrast to the free anticancer drug, the prodrug exhibited higher cytotoxicity to hepatoma cells than that to normal HL-7702 cells. Thus, prodrug 4 is a promising platform for specific tumor-activatable drug delivery system, because of its favorable features of in situ and in vivo monitoring of the drug release and therapeutic efficacy.
为了降低化疗的副作用，迫切需要使用肿瘤微环境激活的无毒前药来治疗癌症。在这项工作中，我们开发了前药 4，用于肿瘤靶向治疗和体内抗癌药物释放的成像。利用癌细胞中高浓度的谷胱甘肽（GSH），前药 4 中的二硫键被切断，导致活性抗癌药物的释放和近红外（NIR）荧光染料的开启。此外，与游离抗癌药物相比，前药对肝癌细胞的细胞毒性高于对正常 HL-7702 细胞的毒性。因此，前药 4 是一种很有前途的特异性肿瘤激活药物传递系统平台，因为它具有原位和体内监测药物释放和治疗效果的有利特征。
