抗辐射性
辐射敏感性
癌症研究
放射治疗
缺氧(环境)
肿瘤缺氧
化学
生物
医学
氧气
内科学
有机化学
作者
Yong Yuan,Chunfang Zhang,Zhennan Gu,Jiangfeng Du,Zhao Guo,Xinghua Dong,Jiani Xie,Guangjin Zhang,Xiangfeng Liu,Ye Zhao
出处
期刊:ACS Nano
[American Chemical Society]
日期:2017-06-26
卷期号:11 (7): 7164-7176
被引量:163
标识
DOI:10.1021/acsnano.7b03037
摘要
Radioresistance is one of the undesirable impediments in hypoxic tumors, which sharply diminishes the therapeutic effectiveness of radiotherapy and eventually results in the failure of their treatments. An attractive strategy for attenuating radioresistance is developing an ideal radiosensitization system with appreciable radiosensitization capacity to attenuate tumor hypoxia and reinforce radiotherapy response in hypoxic tumors. Therefore, we describe the development of Gd-containing polyoxometalates-conjugated chitosan (GdW10@CS nanosphere) as a radiosensitization system for simultaneous extrinsic and intrinsic radiosensitization, by generating an overabundance of cytotoxic reactive oxygen species (ROS) using high-energy X-ray stimulation and mediating the hypoxia-inducible factor-1a (HIF-1a) siRNA to down-regulate HIF-1α expression and suppress broken double-stranded DNA self-healing. Most importantly, the GdW10@CS nanospheres have the capacity to promote the exhaustion of intracellular glutathione (reduced GSH) by synergy W6+-triggered GSH oxidation for sufficient ROS generation, thereby facilitating the therapeutic efficiency of radiotherapy. As a result, the as-synthesized GdW10@CS nanosphere can overcome radioresistance of hypoxic tumors through a simultaneous extrinsic and intrinsic strategy to improve radiosensitivity. We have demonstrated GdW10@CS nanospheres with special radiosensitization behavior, which provides a versatile approach to solve the critical radioresistance issue of hypoxic tumors.
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