TY - JOUR
T1 - Fractionated regimen-suitable immunoradiotherapy sensitizer based on ultrasmall Fe4Se2W18 nanoclusters enable tumor-specific radiosensitization augment and antitumor immunity boost
AU - Zhou, Ruyi
AU - Yan, Liang
AU - Dong, Xinghua
AU - Zhu, Shuang
AU - Chen, Kui
AU - Wu, Yuanzheng
AU - Xiang, Huandong
AU - Li, Lele
AU - Zhang, Guangjin
AU - Gu, Zhanjun
AU - Zhao, Yuliang
N1 - Funding Information:
We greatly acknowledge the financial support from S trategic Priority Research Program of Chinese Academy of Sciences ( XDB36000000), N ational Basic Research Program of China ( 2016YFA0201600) , National Natural Science Foundation of China ( 51822207 , 51772292 , 11621505 , and 31700866 ), Y outh Innovation Promotion Association CAS ( 2013007), and I nnovation Program of the Chinese Academy of Science ( QYZDJ-SSW-SLH022) . R. Zhou and L. Yan contributed equally to this work.
Funding Information:
We greatly acknowledge the financial support from Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000), National Basic Research Program of China (2016YFA0201600), National Natural Science Foundation of China (51822207, 51772292, 11621505, and 31700866), Youth Innovation Promotion Association CAS (2013007), and Innovation Program of the Chinese Academy of Science (QYZDJ-SSW-SLH022). R. Zhou and L. Yan contributed equally to this work.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2021/2
Y1 - 2021/2
N2 - Immunoradiotherapy involving the combination of spatial control of radiotherapy and systemic survival of immunotherapy together has emerged as a promising strategy for both local and systemic tumor rejection. However, immunoradiotherapeutic efficacy is highly impeded by the radiation-induced immunosuppression and the insufficiency of antitumor immunity. Herein, ultrasmall Sandwich-type polyoxotungstate nanoclusters (Fe4Se2W18 NCs) with abundant high Z elements, efficient catalytic property, and unique electron structure are designed as the immunoradio-sensitizers. Apart from enhancing X-ray deposition for dose reduction, Fe4Se2W18 NCs exhibit tumor microenvironment-responsive catalytic activity, mainly through GSH depletion and Fenton reaction. Upon X-ray irradiation, Fe4Se2W18 NCs generate hydroxyl radical cascade to elevate tumor-specific oxidative stress, which can not only selectively ablate the local tumor but also effectively activate antitumor immune response. More importantly, ultrasmall Fe4Se2W18 NCs can be rapidly eliminated from the body, which can satisfy the needs of the fractionated regimen of radiotherapy clinically to reduce radiation-induced immunosuppression. Immune checkpoint inhibitor (anti-PD-L1 antibody) is further introduced into this system to boost a robust antitumor immunity, resulting in the inhibition of both primary and distant tumors. By presenting the Sandwich-type polyoxotungstate nanoclusters for immunoradiotherapy augmentation, this study is anticipated to establish a novel paradigm for immunoradio-sensitizer design based on polyoxometalate nanoclusters.
AB - Immunoradiotherapy involving the combination of spatial control of radiotherapy and systemic survival of immunotherapy together has emerged as a promising strategy for both local and systemic tumor rejection. However, immunoradiotherapeutic efficacy is highly impeded by the radiation-induced immunosuppression and the insufficiency of antitumor immunity. Herein, ultrasmall Sandwich-type polyoxotungstate nanoclusters (Fe4Se2W18 NCs) with abundant high Z elements, efficient catalytic property, and unique electron structure are designed as the immunoradio-sensitizers. Apart from enhancing X-ray deposition for dose reduction, Fe4Se2W18 NCs exhibit tumor microenvironment-responsive catalytic activity, mainly through GSH depletion and Fenton reaction. Upon X-ray irradiation, Fe4Se2W18 NCs generate hydroxyl radical cascade to elevate tumor-specific oxidative stress, which can not only selectively ablate the local tumor but also effectively activate antitumor immune response. More importantly, ultrasmall Fe4Se2W18 NCs can be rapidly eliminated from the body, which can satisfy the needs of the fractionated regimen of radiotherapy clinically to reduce radiation-induced immunosuppression. Immune checkpoint inhibitor (anti-PD-L1 antibody) is further introduced into this system to boost a robust antitumor immunity, resulting in the inhibition of both primary and distant tumors. By presenting the Sandwich-type polyoxotungstate nanoclusters for immunoradiotherapy augmentation, this study is anticipated to establish a novel paradigm for immunoradio-sensitizer design based on polyoxometalate nanoclusters.
KW - Abscopal effect
KW - Fenton reaction
KW - Fractionated regimen
KW - Immunoradiotherapy
KW - Oxidative stress
KW - Sandwich-type polyoxotungstate
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U2 - 10.1016/j.nantod.2020.101003
DO - 10.1016/j.nantod.2020.101003
M3 - Article
AN - SCOPUS:85095688382
SN - 1748-0132
VL - 36
JO - Nano Today
JF - Nano Today
M1 - 101003
ER -