Rhenium-188 Labeled Tungsten Disulfide Nanoflakes for Self-Sensitized, Near-Infrared Enhanced Radioisotope Therapy

Small. 2016 Aug;12(29):3967-75. doi: 10.1002/smll.201601375. Epub 2016 Jun 27.

Abstract

Radioisotope therapy (RIT), in which radioactive agents are administered or implanted into the body to irradiate tumors from the inside, is a clinically adopted cancer treatment method but still needs improvement to enhance its performances. Herein, it is found that polyethylene glycol (PEG) modified tungsten disulfide (WS2 ) nanoflakes can be easily labeled by (188) Re, a widely used radioisotope for RIT, upon simple mixing. Like other high-Z elements acting as radiosensitizers, tungsten in the obtained (188) Re-WS2 -PEG would be able to absorb ionization radiation generated from (188) Re, enabling ''self-sensitization'' to enhance the efficacy of RIT as demonstrated in carefully designed in vitro experiments of this study. In the meanwhile, the strong NIR absorbance of WS2 -PEG could be utilized for NIR light-induced photothermal therapy (PTT), which if applied on tumors would be able to greatly relieve their hypoxia state and help to overcome hypoxia-associated radioresistance of tumors. Therefore, with (188) Re-WS2 -PEG as a multifunctional agent, which shows efficient passive tumor homing after intravenous injection, in vivo self-sensitized, NIR-enhanced RIT cancer treatment is realized, achieving excellent tumor killing efficacy in a mouse tumor model. This work presents a new concept of applying nanotechnology in RIT, by delivering radioisotopes into tumors, self-sensitizing the irradiation-induced cell damage, and modulating the tumor hypoxia state to further enhance the therapeutic outcomes.

Keywords: WS2 nanoflakes; photothermal therapy; radioisotope therapy; rhenium-188; self-sensitize.

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / therapy
  • Cell Line, Tumor
  • Disulfides / chemistry*
  • Female
  • Hyperthermia, Induced
  • Immunohistochemistry
  • Mice
  • Mice, Inbred BALB C
  • Photochemotherapy / methods*
  • Radioisotopes / chemistry*
  • Radioisotopes / therapeutic use*
  • Rhenium / chemistry*
  • Tungsten / chemistry*

Substances

  • Disulfides
  • Radioisotopes
  • Rhenium-188
  • Rhenium
  • Tungsten