Peroxynitrite Activated Drug Conjugate Systems Based on a Coumarin Scaffold Toward the Application of Theranostics
Peroxynitrite Activated Drug Conjugate Systems Based on a Coumarin Scaffold Toward the Application of Theranostics
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DOI：
10.3389/fchem.2019.00775
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发表时间：
2019-12-05
影响因子：
5.5
通讯作者：
James, Tony D.
中科院分区：
文献类型：
--
作者：
Odyniec, Maria L.;Han, Hai-Hao;James, Tony D.
设计了两种基于香豆素连接物的新型药物结合物，用于治疗剂和荧光探针的协同释放，为治疗药物的潜在应用奠定了基础。药物结合物CC-RNS和CI-RNS被设计为被活性氧或活性氮(ROS/RNS)激活。荧光关闭-开启反应是由过氧亚硝酸盐介导的硼酸频那醇酯转化为苯酚部分并同时释放治疗剂而触发的(经HRMS证实)。CC-RNS和CI-RNS对过氧亚硝酸根的检出限分别为0.29和37.2µM。CC-RNS和CI-RNS都展示了可视化过氧亚硝酸盐产生的能力，从而证明了这些探针作为工具用于监测过氧亚硝酸盐在癌细胞系中的药物释放的有效性。
Two novel drug-conjugates based on a "coumarin linker" have been designed for the synergic release of a therapeutic agent and fluorescent probe for the potential application of theranostics. The drug conjugates; CC-RNS and CI-RNS were designed to be activated by reactive oxygen species or reactive nitrogen species (ROS/RNS). The fluorescence OFF-ON response was triggered by the peroxynitrite-mediated transformation of a boronic acid pinacol ester to a phenol moiety with simultaneous release of the therapeutic agents (Confirmed by HRMS). The limit of detection for peroxynitrite using CC-RNS and CI-RNS was 0.29 and 37.2 mu M, respectively. Both CC-RNS and CI-RNS demonstrated the ability to visualize peroxynitrite production thus demonstrating the effectiveness of these probes for use as tools to monitor peroxynitrite-mediated drug release in cancer cell lines.