活性氧
杀伤力
光动力疗法
DNA修复
化学
氧气
医学
单线态氧
合成致死
光敏剂
癌症研究
DNA
生物
生物物理学
癌症
体内
程序性细胞死亡
药理学
生物化学
毒理
有机化学
作者
Lingzhi Zhao,Junyao Li,Yaoquan Su,Liqiang Yang,Liu Chen,Qiang Liu,Yajing Wang,Huijing Xiang,Huijun Phoebe Tham,Juanjuan Peng,Yanli Zhao
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2020-03-06
卷期号:6 (10)
被引量:56
标识
DOI:10.1126/sciadv.aaz0575
摘要
Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein, we developed a strategy to solve the hypoxia issue by enhancing the lethality of ROS. Before PDT, the ROS-defensing system of the cancer cells was obstructed by an inhibitor to MTH1, which is a key for the remediation of ROS-caused DNA damage. As a result, both nuclei and mitochondrial DNA damages were increased, remarkably promoting cellular apoptosis. The therapeutic results demonstrated that the performance of PDT can be improved by the MTH1 inhibitor, leading to efficient cancer cell killing effect in the hypoxic tumor. This strategy makes better use of the limited oxygen, holding the promise to achieve satisfactory therapeutic effect by PDT without generating redundant cytotoxic ROS.
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