Radiat Oncol J.  2016 Sep;34(3):230-238. 10.3857/roj.2016.01788.

Gold nanoparticles enhance anti-tumor effect of radiotherapy to hypoxic tumor

• Kim MS
• Lee EJ
• Kim JW
• Chung US
• Koh WG
• Keum KC
• Koom WS

• KMID: 2356120
• DOI: http://doi.org/10.3857/roj.2016.01788

Abstract

PURPOSE
Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors.
MATERIALS AND METHODS
Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death.
RESULTS
Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished.
CONCLUSION
In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

Keyword

Nanoparticle; Hypoxia; Radiotherapy

MeSH Terms

Animals
Anoxia
Cell Death
Cell Survival
Colonic Neoplasms
DNA Nucleotidylexotransferase
In Vitro Techniques
Mice
Nanoparticles*
Radiotherapy*
Reactive Oxygen Species
Silicon Dioxide
DNA Nucleotidylexotransferase
Reactive Oxygen Species
Silicon Dioxide