Chen Zelin, Li Bowen, Xie Xin, Zeng Fang, Wu Shuizhu
State Key Lab of Luminescent Materials & Devices, College of Materials Science & Engineering, South China University of Technology, Guangzhou 510640, P. R. China.
J Mater Chem B. 2018 May 7;6(17):2547-2556. doi: 10.1039/c7tb01989k. Epub 2017 Sep 18.
DT-diaphorase is a cytosolic flavoenzyme whose level is strongly elevated in a number of tumor types. Incorporating a DT-diaphorase's substrate in the structure of anticancer drugs may facilitate cancer detection and therapy. Herein, we developed a novel pro-prodrug nanosystem for cancer detection and therapy, which features enzyme-activated fluorescence emission and subsequent light-triggered drug release. The pro-prodrug molecule comprises an anticancer drug methotrexate (MTX), an enzyme (DT-diaphorase) responsive quinone propionic acid moiety and a light-activatable coumarinyl. In the absence of DT-diaphorase, the quinone propionic acid moiety quenches the fluorescence of coumarin via photoinduced electron transfer (PET) and blocks the photocleavage pathway. DT-diaphorase can annihilate the effect of PET and restore the fluorescence of coumarin. This fluorescence serves as the reporting signal for assessing the enzyme biomarker level and discriminates tumor cells from normal cells, and subsequently photocontrollable release of the active drug, MTX, can be activated via one- or two-photon irradiation. This pro-prodrug nanosystem shows strong cytotoxicity toward cancer cells and a negligible effect on normal cells. This strategy provides a new platform for constructing nanosystems for cancer detection and subsequent on-demand selective killing of cancer cells via both internal- and external-stimuli activation.
DT-黄递酶是一种胞质黄素酶，其水平在多种肿瘤类型中显著升高。将DT-黄递酶的底物纳入抗癌药物结构中可能有助于癌症检测和治疗。在此，我们开发了一种用于癌症检测和治疗的新型前体药物纳米系统，其特点是酶激活荧光发射以及随后的光触发药物释放。前体药物分子包含抗癌药物甲氨蝶呤（MTX）、一种对酶（DT-黄递酶）有反应的醌丙酸部分和一个可光激活的香豆素基。在没有DT-黄递酶的情况下，醌丙酸部分通过光诱导电子转移（PET）淬灭香豆素的荧光并阻断光裂解途径。DT-黄递酶可以消除PET的作用并恢复香豆素的荧光。这种荧光作为评估酶生物标志物水平的报告信号，可区分肿瘤细胞和正常细胞，随后活性药物MTX的光控释放可通过单光子或双光子照射激活。这种前体药物纳米系统对癌细胞显示出强烈的细胞毒性，对正常细胞的影响可忽略不计。该策略为构建用于癌症检测以及随后通过内部和外部刺激激活按需选择性杀死癌细胞的纳米系统提供了一个新平台。
