Improving 131I radioiodine therapy by hybrid metal-polymer nanoparticles

Introduction 131I radioiodine therapy is very performant in the treatment of thyroid cancer metastases. Applicability of this approach combined with gene therapy (transfer of the Na/I symporter gene into tumors)... [ view full abstract ]

Introduction

¹³¹I radioiodine therapy is very performant in the treatment of thyroid cancer metastases. Applicability of this approach combined with gene therapy (transfer of the Na/I symporter gene into tumors) to treat non-thyroidal neoplasms is still hampered by the reduced capacity of such tumors to accumulate ¹³¹I. Various strategies have been tested so far to improve this approach, with limited efficacy. The use of metal-containing nanoparticles as radiosensitizers for cancer treatment has been reported in the context of External Beam Radiation Therapy. The present study reveals novel information on using these nano-objects to enhance the therapeutic efficacy of ¹³¹I-mediated radiotherapy.

Methods

Various metal-containing nanoparticles were synthesized by reduction of corresponding metal salts. Polymethacrylate acid was grafted onto their surface (information on the poster by Le Goas et al). We performed in vitro clonogenic assays to investigate the impact of the nano-objects on the damage induced by ¹³¹I (0-300 microCi) using melanoma and colorectal cancer cells expressing the Na/I symporter (NIS). Finally, the efficacy of the nanoparticles to sensitize tumors to radio-iodine treatment was explored in a preclinical model of melanoma-bearing mice receiving percutaneous intratumoral injections of Np at 10% of tumor volume.

Results

After incubation with the gold nanoparticles for 2 hours, marked radiosensitization was observed on the melanoma and colorectal cancer cells exposed to 10 microCi ¹³¹I. In vivo, intratumoral injections of PMAA-GNP combined with systemic ¹³¹I treatment led to a reduction in melanoma B16 tumor development compared to radio-iodine alone. Histological analysis shows increased cell death in tumors treated with combined therapies compared to radiotherapy alone.

Discussion

All together, these results open up novel perspectives for using high-Z metallic NPs in radiotherapy.