体外和体内无创实时报告药物释放
Non-invasive, real-time reporting drug release in vitro and in vivo.
作者信息
Zhang Yanfeng, Yin Qian, Yen Jonathan, Li Joanne, Ying Hanze, Wang Hua, Hua Yuyan, Chaney Eric J, Boppart Stephen A, Cheng Jianjun
机构信息
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 West Green Street, Urbana, IL 61801, USA.
出版信息
Chem Commun (Camb). 2015 Apr 25;51(32):6948-51. doi: 10.1039/c4cc09920f. Epub 2015 Mar 23.
Abstract
We developed a real-time drug-reporting conjugate (CPT-SS-CyN) composed of a near-infrared (NIR) fluorescent cyanine-amine dye (CyN), a disulfide linker, and a model therapeutic drug (camptothecin, CPT). Treatment with dithiothreitol (DTT) induces cleavage of the disulfide bond, followed by two simultaneous intramolecular cyclization reactions with identical kinetics, one to cleave the urethane linkage to release the NIR dye and the other to cleave the carbonate linkage to release CPT. The released CyN has an emission wavelength (760 nm) that is significantly different from CPT-SS-CyN (820 nm), enabling easy detection and monitoring of drug release. A linear relationship between the NIR fluorescence intensity at 760 nm and the amount of CPT released was observed, substantiating the use of this drug-reporting conjugate to enable precise, real-time, and non-invasive quantitative monitoring of drug release in live cells and semi-quantitative monitoring in live animals.
摘要
我们开发了一种实时药物报告共轭物（CPT-SS-CyN），它由近红外（NIR）荧光花菁胺染料（CyN）、二硫键连接子和一种模型治疗药物（喜树碱，CPT）组成。用二硫苏糖醇（DTT）处理会诱导二硫键断裂，随后发生两个具有相同动力学的同时进行的分子内环化反应，一个反应会切断氨基甲酸酯连接以释放近红外染料，另一个反应会切断碳酸酯连接以释放CPT。释放出的CyN具有与CPT-SS-CyN（820 nm）显著不同的发射波长（760 nm），从而能够轻松检测和监测药物释放。观察到760 nm处的近红外荧光强度与释放的CPT量之间存在线性关系，证实了使用这种药物报告共轭物能够在活细胞中进行精确、实时和非侵入性的药物释放定量监测，并在活体动物中进行半定量监测。
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