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Title: Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures

Abstract

Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide TiO2, as a radio-sensitizer for radiation therapy of triple negative breast cancer (TNBC). In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DATs uptake for a radio-sensitized radiation therapy.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [2];  [2];  [3]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [1]
+ Show Author Affiliations
  1. Stanford Univ., CA (United States). Dept. of Radiation Oncology, School of Medicine
  2. SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
  3. Stanford Univ., CA (United States). Molecular Imaging Program at Stanford (MIPS) and Dept. of Radiology
Publication Date:
Research Org.:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1461481
Grant/Contract Number:  
AC02-76SF00515
Resource Type:
Accepted Manuscript
Journal Name:
ACS Nano
Additional Journal Information:
Journal Volume: 12; Journal Issue: 5; Journal ID: ISSN 1936-0851
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES; Radiation/chemo therapy; radio sensitizer; reactive oxygen species; gold-titanium oxide nanoparticles; heterogeneous interface; triple negative breast cancers

Citation Formats

Cheng, Kai, Sano, Michael, Jenkins, Cesare H., Zhang, Guanglei, Vernekohl, Don, Zhao, Wei, Wei, Chenxi, Zhang, Yan, Zhang, Zhe, Liu, Yijin, Cheng, Zhen, and Xing, Lei. Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures. United States: N. p., 2018. Web. doi:10.1021/acsnano.8b02038.
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Cheng, Kai, Sano, Michael, Jenkins, Cesare H., Zhang, Guanglei, Vernekohl, Don, Zhao, Wei, Wei, Chenxi, Zhang, Yan, Zhang, Zhe, Liu, Yijin, Cheng, Zhen, & Xing, Lei. Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures. United States. https://doi.org/10.1021/acsnano.8b02038
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Cheng, Kai, Sano, Michael, Jenkins, Cesare H., Zhang, Guanglei, Vernekohl, Don, Zhao, Wei, Wei, Chenxi, Zhang, Yan, Zhang, Zhe, Liu, Yijin, Cheng, Zhen, and Xing, Lei. Tue . "Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures". United States. https://doi.org/10.1021/acsnano.8b02038. https://www.osti.gov/servlets/purl/1461481.
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@article{osti_1461481,
title = {Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures},
author = {Cheng, Kai and Sano, Michael and Jenkins, Cesare H. and Zhang, Guanglei and Vernekohl, Don and Zhao, Wei and Wei, Chenxi and Zhang, Yan and Zhang, Zhe and Liu, Yijin and Cheng, Zhen and Xing, Lei},
abstractNote = {Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide TiO2, as a radio-sensitizer for radiation therapy of triple negative breast cancer (TNBC). In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DATs uptake for a radio-sensitized radiation therapy.},
doi = {10.1021/acsnano.8b02038},
journal = {ACS Nano},
number = 5,
volume = 12,
place = {United States},
year = {2018},
month = {4}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1021/acsnano.8b02038
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Figures / Tables:

Figure 1 Figure 1: Radiation activatable and reactive oxygen species-releasing nanostructures. Schematic illustration of the formation of superoxide (·O2-) and hydroxyl radical (·OH) on photo-excited TiO2 NPs (A) and X-ray induced hybrid DATs (B). (C) TEM image of Au NPs. (D) TEM image34 of TiO2 NPs. (E) TEM image of DATs. (F-H),more » representative TEM images of DATs in different magnifications. (I) High resolution TEM image of the interface between an Au and TiO2 NP. Inset: Au (111) lattice spacing = 0.236 nm. (J) Energy-dispersive X-ray spectroscopy (EDX) analysis of DATs. (K) hydrodynamic sizes of Au NPs and DATs.« less
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