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

Yuan Yong, Chunfang Zhang, Zhanjun Gu, Jiangfeng Du, Zhao Guo, Xinghua Dong, Jiani Xie, Guangjin Zhang, Xiangfeng Liu, Yuliang Zhao

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7164-7176
Number of pages13
JournalACS Nano
Volume11
Issue number7
DOIs
StatePublished - Jul 25 2017

Keywords

  • GdW@CS nanosphere
  • gene therapy
  • glutathione
  • hypoxic tumor
  • polyoxometalates
  • radiosensitization
  • radiotherapy

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Fingerprint

Dive into the research topics of 'Polyoxometalate-Based Radiosensitization Platform for Treating Hypoxic Tumors by Attenuating Radioresistance and Enhancing Radiation Response'. Together they form a unique fingerprint.

Cite this