DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

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]
  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 Lab., 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.
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
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.
@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}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 16 works
Citation information provided by
Web of Science

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

Save / Share:

Works referenced in this record:

Strategies to improve radiotherapy with targeted drugs
journal, March 2011

  • Begg, Adrian C.; Stewart, Fiona A.; Vens, Conchita
  • Nature Reviews Cancer, Vol. 11, Issue 4
  • DOI: 10.1038/nrc3007

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice
journal, July 2014


Radiation therapy primes tumors for nanotherapeutic delivery via macrophage-mediated vascular bursts
journal, May 2017

  • Miller, Miles A.; Chandra, Ravi; Cuccarese, Michael F.
  • Science Translational Medicine, Vol. 9, Issue 392
  • DOI: 10.1126/scitranslmed.aal0225

Cancer Nanomedicine: From Drug Delivery to Imaging
journal, December 2013


Nanoparticles for Radiation Therapy Enhancement: the Key Parameters
journal, January 2015

  • Retif, Paul; Pinel, Sophie; Toussaint, Magali
  • Theranostics, Vol. 5, Issue 9
  • DOI: 10.7150/thno.11642

Scintillating Nanoparticles as Energy Mediators for Enhanced Photodynamic Therapy
journal, April 2016


Nanoparticles in radiation oncology: From bench-side to bedside
journal, June 2016


Key clinical beam parameters for nanoparticle-mediated radiation dose amplification
journal, September 2016

  • Detappe, Alexandre; Kunjachan, Sijumon; Drané, Pascal
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep34040

Roadmap to Clinical Use of Gold Nanoparticles for Radiation Sensitization
journal, January 2016

  • Schuemann, Jan; Berbeco, Ross; Chithrani, Devika B.
  • International Journal of Radiation Oncology*Biology*Physics, Vol. 94, Issue 1
  • DOI: 10.1016/j.ijrobp.2015.09.032

Harnessing the Power of Nanotechnology for Enhanced Radiation Therapy
journal, May 2017


Nanoscale Energy Deposition by X-ray Absorbing Nanostructures
journal, October 2007

  • Carter, Joshua D.; Cheng, Neal N.; Qu, Yongquan
  • The Journal of Physical Chemistry B, Vol. 111, Issue 40
  • DOI: 10.1021/jp075253u

X-ray-Induced Energy Transfer between Nanomaterials under X-ray Irradiation
journal, February 2016


Multiplication Algorithm for Combined Physical and Chemical Enhancement of X-ray Effect by Nanomaterials
journal, August 2015


Chemical Enhancement by Nanomaterials under X-ray Irradiation
journal, January 2012

  • Cheng, Neal N.; Starkewolf, Zane; Davidson, R. Andrew
  • Journal of the American Chemical Society, Vol. 134, Issue 4
  • DOI: 10.1021/ja210239k

Designing Core–Shell Gold and Selenium Nanocomposites for Cancer Radiochemotherapy
journal, April 2017


Construction and Validation of Nano Gold Tripods for Molecular Imaging of Living Subjects
journal, February 2014

  • Cheng, Kai; Kothapalli, Sri-Rajasekhar; Liu, Hongguang
  • Journal of the American Chemical Society, Vol. 136, Issue 9
  • DOI: 10.1021/ja412001e

Janus Au-TiO 2 Photocatalysts with Strong Localization of Plasmonic Near-Fields for Efficient Visible-Light Hydrogen Generation
journal, March 2012


Anisotropic Growth of Titania onto Various Gold Nanostructures: Synthesis, Theoretical Understanding, and Optimization for Catalysis
journal, September 2011

  • Seh, Zhi Wei; Liu, Shuhua; Zhang, Shuang-Yuan
  • Angewandte Chemie International Edition, Vol. 50, Issue 43
  • DOI: 10.1002/anie.201104943

Titania-Coated Metal Nanostructures
journal, June 2012

  • Seh, Zhi Wei; Liu, Shuhua; Han, Ming-Yong
  • Chemistry - An Asian Journal, Vol. 7, Issue 10
  • DOI: 10.1002/asia.201200265

Titanium and Zinc Oxide Nanoparticles Are Proton-Coupled Electron Transfer Agents
journal, June 2012


Titania supported gold nanoparticles as photocatalyst
journal, January 2011

  • Primo, Ana; Corma, Avelino; García, Hermenegildo
  • Phys. Chem. Chem. Phys., Vol. 13, Issue 3
  • DOI: 10.1039/C0CP00917B

Breaking the depth dependency of phototherapy with Cerenkov radiation and low-radiance-responsive nanophotosensitizers
journal, March 2015

  • Kotagiri, Nalinikanth; Sudlow, Gail P.; Akers, Walter J.
  • Nature Nanotechnology, Vol. 10, Issue 4
  • DOI: 10.1038/nnano.2015.17

Dual-Wavelength Irradiation and Dox Delivery for ­Cancer Cell Ablation with Photocatalytic Pr Doped TiO 2 /NGO ­Hybrid Nanocomposite
journal, June 2015

  • Jang, Hongje; Choi, Myung-Ho; Yim, Yeajee
  • Advanced Healthcare Materials, Vol. 4, Issue 12
  • DOI: 10.1002/adhm.201500157

Titania Coated Upconversion Nanoparticles for Near-Infrared Light Triggered Photodynamic Therapy
journal, January 2015

  • Lucky, Sasidharan Swarnalatha; Muhammad Idris, Niagara; Li, Zhengquan
  • ACS Nano, Vol. 9, Issue 1
  • DOI: 10.1021/nn503450t

Anisotropic Growth of TiO 2 onto Gold Nanorods for Plasmon-Enhanced Hydrogen Production from Water Reduction
journal, January 2016

  • Wu, Binghui; Liu, Deyu; Mubeen, Syed
  • Journal of the American Chemical Society, Vol. 138, Issue 4
  • DOI: 10.1021/jacs.5b11341

Direct Evidence of Chelated Geometry of Catechol on TiO 2 by a Combined Solid-State NMR and DFT Study
journal, October 2016

  • Finkelstein-Shapiro, Daniel; Davidowski, Stephen K.; Lee, Paul B.
  • The Journal of Physical Chemistry C, Vol. 120, Issue 41
  • DOI: 10.1021/acs.jpcc.6b08041

Porous Hollow Fe 3 O 4 Nanoparticles for Targeted Delivery and Controlled Release of Cisplatin
journal, August 2009

  • Cheng, Kai; Peng, Sheng; Xu, Chenjie
  • Journal of the American Chemical Society, Vol. 131, Issue 30
  • DOI: 10.1021/ja903300f

Effect of Ceria on Gold–Titania Catalysts for the Water–Gas Shift Reaction: Fundamental Studies for Au/CeO x /TiO 2 (110) and Au/CeO x /TiO 2 Powders
journal, October 2012

  • Si, Rui; Tao, Jing; Evans, Jaime
  • The Journal of Physical Chemistry C, Vol. 116, Issue 44
  • DOI: 10.1021/jp3089325

The effect of sedimentation and diffusion on cellular uptake of gold nanoparticles
journal, April 2011

  • Cho, Eun Chul; Zhang, Qiang; Xia, Younan
  • Nature Nanotechnology, Vol. 6, Issue 6
  • DOI: 10.1038/nnano.2011.58

Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations
journal, January 2012


The Fate and Toxicity of Raman-Active Silica-Gold Nanoparticles in Mice
journal, April 2011


Hybrid Nanotrimers for Dual T 1 and T 2 -Weighted Magnetic Resonance Imaging
journal, October 2014

  • Cheng, Kai; Yang, Meng; Zhang, Ruiping
  • ACS Nano, Vol. 8, Issue 10
  • DOI: 10.1021/nn500188y

The One Year Fate of Iron Oxide Coated Gold Nanoparticles in Mice
journal, July 2015


Advances in Image-Guided Radiation Therapy
journal, March 2007


Strategies for optimizing the response of cancer and normal tissues to radiation
journal, July 2013

  • Moding, Everett J.; Kastan, Michael B.; Kirsch, David G.
  • Nature Reviews Drug Discovery, Vol. 12, Issue 7
  • DOI: 10.1038/nrd4003

Average Physical Enhancement by Nanomaterials under X-ray Irradiation
journal, December 2014

  • Davidson, R. Andrew; Guo, Ting
  • The Journal of Physical Chemistry C, Vol. 118, Issue 51
  • DOI: 10.1021/jp509471m

Metal/Semiconductor Hybrid Nanostructures for Plasmon-Enhanced Applications
journal, April 2014


Protein:Colloid Conjugates for Surface Enhanced Raman Scattering:  Stability and Control of Protein Orientation
journal, November 1998

  • Keating, Christine D.; Kovaleski, Kenneth M.; Natan, Michael J.
  • The Journal of Physical Chemistry B, Vol. 102, Issue 47
  • DOI: 10.1021/jp982723z

Works referencing / citing this record:

X-ray-activated nanosystems for theranostic applications
journal, January 2019

  • Chen, Xiaofeng; Song, Jibin; Chen, Xiaoyuan
  • Chemical Society Reviews, Vol. 48, Issue 11
  • DOI: 10.1039/c8cs00921j

Facile green synthesis of bismuth sulfide radiosensitizer via biomineralization of albumin natural molecule for chemoradiation therapy aim
journal, September 2019

  • Nosrati, Hamed; Abhari, Fatemeh; Charmi, Jalil
  • Artificial Cells, Nanomedicine, and Biotechnology, Vol. 47, Issue 1
  • DOI: 10.1080/21691401.2019.1669624

Anisotropic Gold Nanoparticles in Biomedical Applications
journal, October 2018

  • Kohout, Claudia; Santi, Cristina; Polito, Laura
  • International Journal of Molecular Sciences, Vol. 19, Issue 11
  • DOI: 10.3390/ijms19113385

Excretable Lanthanide Nanoparticle for Biomedical Imaging and Surgical Navigation in the Second Near‐Infrared Window
journal, September 2019


Radionuclide 188 Re‐Loaded Photothermal Hydrogel for Cancer Theranostics
journal, January 2020

  • Wang, Yangyun; Li, Linlin; Shi, Xingpeng
  • Particle & Particle Systems Characterization, Vol. 37, Issue 2
  • DOI: 10.1002/ppsc.201900421

An Ultrasound Activated Vesicle of Janus Au‐MnO Nanoparticles for Promoted Tumor Penetration and Sono‐Chemodynamic Therapy of Orthotopic Liver Cancer
journal, January 2020

  • Lin, Xiahui; Liu, Shuya; Zhang, Xuan
  • Angewandte Chemie International Edition, Vol. 59, Issue 4
  • DOI: 10.1002/anie.201912768

Energy‐Converting Nanomedicine
journal, February 2019


Exogenous Physical Irradiation on Titania Semiconductors: Materials Chemistry and Tumor-Specific Nanomedicine
journal, October 2018


A gold nanoparticle system for the enhancement of radiotherapy and simultaneous monitoring of reactive-oxygen-species formation
journal, October 2018


Breaking the Depth Dependence by Nanotechnology‐Enhanced X‐Ray‐Excited Deep Cancer Theranostics
journal, January 2019


Bovine serum albumin stabilized iron oxide and gold bimetallic heterodimers: Synthesis, characterization and Stereological study
journal, August 2019

  • Nosrati, Hamed; Davaran, Soodabeh; Kheiri Manjili, Hamidreza
  • Applied Organometallic Chemistry, Vol. 33, Issue 10
  • DOI: 10.1002/aoc.5155

Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.