Liu Yang, Pei Qing, Chen Li, Li Zhensheng, Xie Zhigang
Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun 130024, P. R. China.
J Mater Chem B. 2016 Apr 7;4(13):2332-2337. doi: 10.1039/c6tb00009f. Epub 2016 Mar 15.
A reduction-responsive fluorescence off-on theranostic prodrug with self-reporting drug release was constructed based on boron dipyrromethene (BODIPY) and therapeutic drug camptothecin (CPT) with a long flexible disulfide linker. Treatment with dithiothreitol (DTT) induced cleavage of the disulfide bond, followed by intramolecular cyclization reaction to release free CPT, simultaneously perturbing electronic energy transfer (EET) and resulting in enhanced blue and green fluorescence emissions. The changes of the fluorescence ratio over time provided the opportunity for detection and real-time monitoring of drug release at the cellular levels. In addition, the disulfide-linked dyad composed of hydrophobic molecules could self-assemble into stable nanoparticles in aqueous solution, facilitating drug delivery and cancer therapy in vivo due to the enhanced permeation and retention (EPR) effect. Nanomedicines displayed similar fluorescence enhancement in tumor cells. These findings confirm that this dye-disulfide-drug system (DDD) has a significant potential for thiol-activated cancer theranostic and self-reporting drug release in a clinical setting.
基于硼二吡咯亚甲基（BODIPY）和治疗药物喜树碱（CPT）构建了一种具有自报告药物释放功能的还原响应型荧光开-关诊疗前药，其带有一个长的柔性二硫键连接子。用二硫苏糖醇（DTT）处理会诱导二硫键断裂，随后发生分子内环化反应以释放游离的CPT，同时干扰电子能量转移（EET）并导致蓝色和绿色荧光发射增强。荧光比率随时间的变化为在细胞水平检测和实时监测药物释放提供了机会。此外，由疏水分子组成的二硫键连接二元体在水溶液中可自组装成稳定的纳米颗粒，由于增强的渗透和滞留（EPR）效应，有助于体内药物递送和癌症治疗。纳米药物在肿瘤细胞中表现出类似的荧光增强。这些发现证实，这种染料-二硫键-药物系统（DDD）在临床环境中具有用于硫醇激活的癌症诊疗和自报告药物释放的巨大潜力。
