A sequential enzyme-activated and light-triggered pro-prodrug nanosystem for cancer detection and therapy,Journal of Materials Chemistry B

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A sequential enzyme-activated and light-triggered pro-prodrug nanosystem for cancer detection and therapy
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2017-09-05 00:00:00 , DOI: 10.1039/c7tb01989k
Zelin Chen _{1,

2,

3,

4,

5} , Bowen Li _{1,

2,

3,

4,

5} , Xin Xie _{1,

2,

3,

4,

5} , Fang Zeng _{1,

2,

3,

4,

5} , Shuizhu Wu _{1,

2,

3,

4,

5}

Affiliation

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.

中文翻译：

用于癌症检测和治疗的顺序酶激活和光触发前药纳米系统

DT-心肌黄递酶是一种胞质黄素酶，在许多类型的肿瘤中其水平都显着升高。在抗癌药物的结构中掺入DT-黄递酶的底物可能有助于癌症的检测和治疗。本文中，我们开发了一种用于癌症检测和治疗的新型前药纳米系统，其特征在于酶激活的荧光发射和随后的光触发药物释放。前药分子包含抗癌药甲氨蝶呤（MTX），酶（DT-diaphorase）响应醌丙酸部分和可光活化的香豆素。在不存在DT-黄递酶的情况下，醌丙酸部分可通过以下方式猝灭香豆素的荧光光诱导电子转移（PET）并阻止光裂解途径。DT-心肌黄递酶可以消除PET的作用并恢复香豆素的荧光。该荧光用作评估酶生物标志物水平的报告信号，并将肿瘤细胞与正常细胞区分开，随后可通过一光子或两光子照射激活活性药物MTX的光控释放。这种前药纳米系统对癌细胞具有很强的细胞毒性，对正常细胞的影响可忽略不计。该策略为构建纳米系统提供了一个新平台，用于通过内部和外部刺激激活来检测癌症以及随后按需选择性杀死癌细胞。

更新日期：2017-09-18

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