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Polyoxometalate-Based Radiosensitization Platform for Treating Hypoxic Tumors by Attenuating Radioresistance and Enhancing Radiation Response

Authors
  • Yong, Yuan
  • Zhang, Chunfang
  • Gu, Zhanjun
  • Du, Jiangfeng
  • Guo, Zhao
  • Dong, Xinghua
  • Xie, Jiani
  • Zhang, Guangjin
  • Liu, Xiangfeng
  • Zhao, Yuliang
Publication Date
Jul 01, 2017
Source
Institutional Repository of Institute of Process Engineering, CAS (IPE-IR)
Keywords
License
Unknown
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Abstract

<p>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 ([email protected] nanosphere) as a radio sensitization 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-la (HIF-la) siRNA to down-regulate HIF-la expression and suppress broken double-stranded DNA self-healing. Most importantly, the [email protected] 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 [email protected] nanosphere can overcome radioresistance of hypoxic tumors through a simultaneous extrinsic and intrinsic strategy to improve radiosensitivity. We have demonstrated [email protected] nanospheres with special radiosensitization behavior, which provides a versatile approach to solve the critical radioresistance issue of hypoxic tumors.</p>

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