TY - JOUR
T1 - Stimuli-Responsive Small-on-Large Nanoradiosensitizer for Enhanced Tumor Penetration and Radiotherapy Sensitization
AU - Fu, Wenhui
AU - Zhang, Xiao
AU - Mei, Linqiang
AU - Zhou, Ruyi
AU - Yin, Wenyan
AU - Wang, Qiang
AU - Gu, Zhanjun
AU - Zhao, Yuliang
N1 - Funding Information:
This work was supported by the National Basic Research Programs of China (2016YFA0201600), National Natural Science Foundation of China (51772293, U1932112, 51772292, 11621505, and 51822207), Beijing Natural Science Foundation (2202064), China Postdoctoral Science Foundation (2019M660794), and CAS Key Laboratory of Nano-Bio Interface (20NBI01).
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/8/25
Y1 - 2020/8/25
N2 - Development of an efficient nanoradiosensitization system that enhances the radiation doses in cancer cells to sensitize radiotherapy (RT) while sparing normal tissues is highly desirable. Here, we construct a tumor microenvironment (TME)-responsive disassembled small-on-large molybdenum disulfide/hafnium dioxide (MoS2/HfO2) dextran (M/H-D) nanoradiosensitizer. The M/H-D can degrade and release the HfO2 nanoparticles (NPs) in TME to enhance tumor penetration of the HfO2 NPs upon near-infrared (NIR) exposure, which can solve the bottleneck of insufficient internalization of the HfO2 NPs. Simultaneously, the NIR photothermal therapy increased peroxidase-like catalytic efficiency of the M/H-D nanoradiosensitizer in TME, which selectively catalyzed intratumorally overexpressed H2O2 into highly oxidized hydroxyl radicals (·OH). The heat induced by PTT also relieved the intratumoral hypoxia to sensitize RT. Consequently, this TME-responsive precise nanoradiosensitization achieved improved irradiation effectiveness, potent oxygenation in tumor, and efficient suppression to tumor, which can be real-time monitored by computed tomography and photoacoustic imaging.
AB - Development of an efficient nanoradiosensitization system that enhances the radiation doses in cancer cells to sensitize radiotherapy (RT) while sparing normal tissues is highly desirable. Here, we construct a tumor microenvironment (TME)-responsive disassembled small-on-large molybdenum disulfide/hafnium dioxide (MoS2/HfO2) dextran (M/H-D) nanoradiosensitizer. The M/H-D can degrade and release the HfO2 nanoparticles (NPs) in TME to enhance tumor penetration of the HfO2 NPs upon near-infrared (NIR) exposure, which can solve the bottleneck of insufficient internalization of the HfO2 NPs. Simultaneously, the NIR photothermal therapy increased peroxidase-like catalytic efficiency of the M/H-D nanoradiosensitizer in TME, which selectively catalyzed intratumorally overexpressed H2O2 into highly oxidized hydroxyl radicals (·OH). The heat induced by PTT also relieved the intratumoral hypoxia to sensitize RT. Consequently, this TME-responsive precise nanoradiosensitization achieved improved irradiation effectiveness, potent oxygenation in tumor, and efficient suppression to tumor, which can be real-time monitored by computed tomography and photoacoustic imaging.
KW - enhanced tumor penetration
KW - intratumoral biodegradation and disassembly
KW - nanoradiosensitization
KW - stimuli response
KW - synergistic therapies
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U2 - 10.1021/acsnano.0c03094
DO - 10.1021/acsnano.0c03094
M3 - Article
C2 - 32658453
AN - SCOPUS:85090076559
SN - 1936-0851
VL - 14
SP - 10001
EP - 10017
JO - ACS Nano
JF - ACS Nano
IS - 8
ER -