通过前药的双重激活实现可见光控制的抗癌药物释放。
Visible Light Controlled Release of Anticancer Drug through Double Activation of Prodrug.
作者信息
Hossion Abugafar M L, Bio Moses, Nkepang Gregory, Awuah Samuel G, You Youngjae
机构信息
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73117, United States.
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73117, United States ; Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
出版信息
ACS Med Chem Lett. 2012 Nov 21;4(1):124-7. doi: 10.1021/ml3003617. eCollection 2013 Jan 10.
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.
我们设计并合成了一种新型双可激活前药系统（药物-连接子-失活光敏剂），其包含一个可光裂解的氨基丙烯酸酯连接子和一种失活光敏剂，以利用可见光实现母体药物的时空可控释放。制备了CA-4、SN-38和香豆素的三种前药，以证明失活光敏剂被细胞酯酶激活以及母体药物通过光去点击化学被可见光（540 nm）释放。在这些前药中，无毒的香豆素前药用于定量活细胞中母体药物的释放。在用MCF-7细胞孵育24小时后，再用低强度可见光（8 mW/cm²）照射30分钟，约99%的香豆素从前药中释放出来。CA-4和SN-38的低毒前药在双重激活后对癌细胞的杀伤效果与游离药物一样有效。
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