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

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 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.

Keywords: Glutathione depletion; Polyoxometalates; Radiocatalytic sensitizer; Reactive oxygen species generation; Tumor microenvironment-manipulation.