Improving ¹³¹I Radioiodine Therapy By Hybrid Polymer-Grafted Gold Nanoparticles

Abstract

Background

Human trials combining external radiotherapy (RT) and metallic nanoparticles are currently underway in cancer patients. For internal RT, in which a radioisotope such as radioiodine is systemically administered into patients, there is also a need for enhancing treatment efficacy, decreasing radiation-induced side effects and overcoming radio-resistance. However, if strategies vectorising radioiodine through nanocarriers have been documented, sensitizing the neoplasm through the use of nanotherapeutics easily translatable to the clinic in combination with the standard systemic radioiodine treatment has not been assessed yet.

Method and materials

The present study explored the potential of hybrid poly(methacrylic acid)-grafted gold nanoparticles to improve the performances of systemic ¹³¹I-mediated RT on cancer cells and in tumor-bearing mice. Such nanoparticles were chosen based on their ability previously described by our group to safely withstand irradiation doses while exhibiting good biocompatibility and enhanced cellular uptake.

Results

In vitro clonogenic assays performed on melanoma and colorectal cancer cells showed that poly(methacrylic acid)-grafted gold nanoparticles (PMAA-AuNPs) could efficiently lead to a marked tumor cell mortality when combined to a low activity of radioiodine, which alone appeared to be essentially ineffective on tumor cells. In vivo, tumor enrichment with PMAA-AuNPs significantly enhanced the killing potential of a systemic radioiodine treatment.

Conclusion

This is the first report of a simple and reliable nanomedicine-based approach to reduce the dose of radioiodine required to reach curability. In addition, these results open up novel perspectives for using high-Z metallic NPs in additional molecular radiation therapy demonstrating heterogeneous dose distributions.

Keywords:

• internal radioisotope therapy
• radioiodine
• polymer-grafted gold nanoparticles
• melanoma
• colorectal cancer
• radio-enhancement

Acknowledgments

This work was supported by INSERM, the French National Research Agency (14IAS001MCSR) and by a grant from CEA (A-PTTOX-02-52-03). The authors thank the radiopharmaceutical team of the Centre Antoine Lacassagne (Nadine Sapin, Guy Martinico, Stéphane Espitallier, Didier Alberato) for their help with radioisotope production and handling. We thank the IRCAN Animal Core Facility for providing access to their equipment. The platform and expertise of the Electron Microscopy Facility of I2BC (Université Paris Sud, CEA-CNRS UMR 9198) is also acknowledged.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Disclosure

Miss Béatrice Cambien reports grants from TIRO laboratory, during the conduct of the study. All authors declare that they have no other conflicts of interest in this work.