Liu Peilian, Li Bowen, Zhan Chenyue, 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. 2017 Sep 28;5(36):7538-7546. doi: 10.1039/c7tb01408b. Epub 2017 Sep 1.
A light-activated cleavage strategy for the concomitant release of active drugs and generation of fluorescence changes is highly desirable. Herein a molecular prodrug featuring real-time monitoring of drug localization and release by manipulating fluorophores has been created by constructing a cleavable structure which comprises a photoremovable coumarinyl, an anticancer drug camptothecin, a cleavable linker and a near infrared fluorescent dye dicyanomethylene-4H-pyran (DCM). The fluorescence of coumarinyl and CPT is completely quenched by the DCM moiety via fluorescence resonance energy transfer (FRET). The internalization of the prodrug by cells and its subsequent intracellular location can be tracked by collecting the red fluorescence of DCM; while the release of active CPT as a result of one- or two-photon irradiation can be monitored by observing the newly emerged fluorescence of CPT under one- or two-photon excitation. The prodrug also shows highly controllable cytotoxicity toward HeLa cells and A549 cells, with low IC values of 4.01 and 2.53 μM, respectively, upon light irradiation and with much higher IC values (>40 μM) without light irradiation. This strategy may provide an approach for the development of light-activatable theranostic anticancer therapeutics.
一种用于同时释放活性药物并产生荧光变化的光激活裂解策略是非常可取的。在此，通过构建一种可裂解结构，创建了一种分子前药，该结构包含一个光可去除香豆素基、一种抗癌药物喜树碱、一个可裂解连接子和一种近红外荧光染料二氰基亚甲基-4H-吡喃（DCM），可通过操纵荧光团对药物定位和释放进行实时监测。香豆素基和喜树碱的荧光通过荧光共振能量转移（FRET）被DCM部分完全淬灭。通过收集DCM的红色荧光可以追踪前药被细胞内化及其随后在细胞内的位置；而在单光子或双光子照射下，通过观察喜树碱在单光子或双光子激发下新出现的荧光，可以监测活性喜树碱的释放。该前药对HeLa细胞和A549细胞也显示出高度可控的细胞毒性，光照下IC值分别低至4.01和2.53 μM，而无光照时IC值则高得多（>40 μM）。该策略可为开发光激活的治疗诊断用抗癌疗法提供一种方法。
