Enhanced Radiotherapy using Bismuth Sulfide Nanoagents Combined with Photo-thermal Treatment

Theranostics. 2017 Sep 20;7(17):4087-4098. doi: 10.7150/thno.20548. eCollection 2017.

Abstract

Nanotechniques that can improve the effectiveness of radiotherapy (RT) by integrating it with multimodal imaging are highly desirable. Results In this study, we fabricated Bi2S3 nanorods that have attractive features such as their ability to function as contrast agents for X-ray computed tomography (CT) and photoacoustic (PA) imaging as well as good biocompatibility. Both in vitro and in vivo studies confirmed that the Bi2S3 nanoagents could potentiate the lethal effects of radiation via amplifying the local radiation dose and enhancing the anti-tumor efficacy of RT by augmenting the photo-thermal effect. Furthermore, the nanoagent-mediated hyperthermia could effectively increase the oxygen concentration in hypoxic regions thereby inhibiting the expression of hypoxia-inducible factor (HIF-1α). This, in turn, interfered with DNA repair via decreasing the expression of DNA repair-related proteins to overcome radio-resistance. Also, RT combined with nanoagent-mediated hyperthermia could substantially suppress tumor metastasis via down-regulating angiogenic factors. Conclusion In summary, we constructed a single-component powerful nanoagent for CT/PA imaging-guided tumor radiotherapy and, most importantly, explored the potential mechanisms of nanoagent-mediated photo-thermal treatment for enhancing the efficacy of RT in a synergistic manner.

Keywords: DNA repair; hypoxia; multimodal imaging; radiation therapy; synergistic therapy..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bismuth / chemistry*
  • Bismuth / therapeutic use
  • Cell Line, Tumor
  • Contrast Media / chemistry*
  • DNA Damage / radiation effects
  • Hyperthermia, Induced / methods
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mice, Inbred BALB C
  • Multimodal Imaging
  • Nanotubes / chemistry*
  • Photoacoustic Techniques / methods
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / pharmacology
  • Radiotherapy, Image-Guided / methods*
  • Sulfides / chemistry*
  • Sulfides / therapeutic use
  • Theranostic Nanomedicine / methods
  • Tomography, X-Ray Computed
  • Xenograft Model Antitumor Assays

Substances

  • Contrast Media
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Radiation-Sensitizing Agents
  • Sulfides
  • Bismuth
  • bismuth sulfide