Tumor microenvironment-manipulated radiocatalytic sensitizer based on bismuth heteropolytungstate for radiotherapy enhancement

Ruyi Zhou, Huamei Wang, Yufei Yang, Chenyang Zhang, Xinghua Dong, Jiangfeng Du, Liang Yan, Guangjin Zhang, Zhanjun Gu, Yuliang Zhao

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

Radioresistance resulted from the intrinsic features of tumors often gives rise to unsatisfied therapeutic outcome. In particular, the tumor microenvironment (TME) with abundant antioxidants, elevated hydrogen peroxide (H2O2) and hypoxia has been believed as a tremendous obstacle for radiotherapy. Therefore, developing an effective radiosensitizer in response to both X-ray and the TME is highly imperative but remains a challenge so far. Here, we for the first time explore bismuth heteropolytungstate (BiP5W30) nanoclusters as radiosensitizers for the TME-manipulated enhancement of radiotherapy. On the one hand, BiP5W30 nanoclusters can increase radiation dose deposition within tumors by high-Z elements like Bi and W. On the other hand, in virtue of the unique electron structure and multi-electron property, they have the capability of depleting glutathione (GSH) via redox reaction and catalyzing the decomposition of H2O2 to HO[rad] to enhance ROS generation upon X-ray radiation. Moreover, reduced graphene oxide (rGO) coupled with BiP5W30 can further improve radiocatalytic activity through promoting electron-hole separation. Simultaneously, due to the considerable near-infrared absorption of rGO, photothermal therapy can overcome the tumor hypoxia microenvironment and thus synergize with radiotherapy. In addition to providing a promising radiosensitizer, this finding is expected to extend the application of polyoxometalates used in the biomedical field.

Original languageEnglish (US)
Pages (from-to)11-22
Number of pages12
JournalBiomaterials
Volume189
DOIs
StatePublished - Jan 2019

Keywords

  • Glutathione depletion
  • Polyoxometalates
  • Radiocatalytic sensitizer
  • Reactive oxygen species generation
  • Tumor microenvironment-manipulation

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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