TY - JOUR
T1 - Tumor microenvironment-manipulated radiocatalytic sensitizer based on bismuth heteropolytungstate for radiotherapy enhancement
AU - Zhou, Ruyi
AU - Wang, Huamei
AU - Yang, Yufei
AU - Zhang, Chenyang
AU - Dong, Xinghua
AU - Du, Jiangfeng
AU - Yan, Liang
AU - Zhang, Guangjin
AU - Gu, Zhanjun
AU - Zhao, Yuliang
N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - Glutathione depletion
KW - Polyoxometalates
KW - Radiocatalytic sensitizer
KW - Reactive oxygen species generation
KW - Tumor microenvironment-manipulation
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U2 - 10.1016/j.biomaterials.2018.10.016
DO - 10.1016/j.biomaterials.2018.10.016
M3 - Article
C2 - 30384125
AN - SCOPUS:85055961634
SN - 0142-9612
VL - 189
SP - 11
EP - 22
JO - Biomaterials
JF - Biomaterials
ER -