Visible Light Controlled Release of Anticancer Drug through Double Activation of Prodrug
Visible Light Controlled Release of Anticancer Drug through Double Activation of Prodrug
复制标题
通过原药的双重活化实现抗癌药物的可见光控制释放
DOI：
10.1021/ml3003617
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发表时间：
2013-01-01
影响因子：
4.2
通讯作者：
You, Youngjae
中科院分区：
文献类型：
--
作者：
Hossion, Abugafar M. L.;Bio, Moses;You, Youngjae
我们设计并合成了一种新型的双可活化前药系统（药物连接体失活光敏剂），其包含可光裂解的氨基丙烯酸酯连接体和失活光敏剂，以实现利用可见光的母体药物的时空控制释放。制备CA-4、SN-38和香豆素的三种前药，以证明细胞酯酶对失活光敏剂的活化以及通过可见光（540 nm）经由光点击化学释放母体药物。在这些前药中，无毒香豆素前药用于定量母体药物在活细胞中的释放。与MCF-7细胞孵育24 h后，约99%的香豆素从香豆素前药中释放，随后用低强度可见光（8 mW/cm（2））照射30 min。毒性较小的CA-4和SN-38前药在双重激活后与游离药物一样有效地杀死癌细胞。
We designed and synthesized a novel double activatable prodrug system (drug linker deactivated photosensitizer), containing a photocleavable aminoacrylate-linker and a deactivated photosensitizer, to achieve the spatiotemporally controlled release of parent drugs using visible light. Three prodrugs of CA-4, SN-38, and coumarin were prepared to demonstrate the activation of deactivated photosensitizer by cellular esterase and the release of parent drugs by visible light (540 nm) via photounclick chemistry. Among these prodrugs, nontoxic coumarin prodrug was used to quantify the release of parent drug in live cells. About 99% coumarin was released from the coumarin prodrug after 24 h of incubation with MCF-7 cells followed by irradiation with low intensity visible light (8 mW/cm(2)) for 30 min. Less toxic prodrugs of CA-4 and SN-38 killed cancer cells as effectively as free drugs after the double activation.