<p>Improving ¹³¹I Radioiodine Therapy By Hybrid Polymer-Grafted Gold Nanoparticles</p>

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 131 I-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.

Nanosystems for Improved Targeted Therapies in Melanoma

“…Le Goas M. et al (2019) improved internal radiotherapy with 131 I by the conjugation of the radioisotope with polymer-grafted AuNPs [71]. The results were promising, with a significant increase in melanoma cell death in vitro and in vivo [71].…”

“…Le Goas M. et al (2019) improved internal radiotherapy with 131 I by the conjugation of the radioisotope with polymer-grafted AuNPs [71]. The results were promising, with a significant increase in melanoma cell death in vitro and in vivo [71]. Daneshvar F. et al (2019) combined X-ray radiotherapy with 808 nm diode laser photothermal therapy of melanoma B16/F10cells after their sensitization with PtNPs [15].…”

Irradiation Effects on Polymer-Grafted Gold Nanoparticles for Cancer Therapy

“…This feature is the object of the in vitro and in vivo studies that will be showed in a forthcoming paper. 30 Overall, the assessed toxicity should be tempered by the conditions used here. Indeed, the incubation time (48 hours) was longer than the average time used elsewhere (see experimental section).…”

“…In a forthcoming paper, more detailed biological effects and particularly, in vitro and in vivo studies will be presented. 30 A covalently grafted polymer corona does not only help to stabilize the nanoparticles (NPs) but it also improves the solubility, the diffusion inside cells, and permits additional effects via the grafting of a therapeutic agent. 31 Here, we synthesized AuNPs with different polymer corona via a "grafting through" or a "direct" process (polymer-AuNPs).…”

“…Polymer-grafted NPs were then studied regarding their biocompatibility (cytotoxicity measurements) before and after irradiation, prior to in vitro and in vivo radiosensitizing studies that will be fully described in a forthcoming paper. 30 Two types of nano-objects were particularly studied: poly(methacrylic acid)-grafted gold nanoparticles (PMAA-AuNPs), and gold nanoparticles coated with poly(hydroxyethyl methacrylate-co-methacrylic acid) (P(HEMA-MAA)-AuNPs), that provided another corona structure, leading to different physico-chemical properties and potential for chemical modification. Indeed, nanoparticles can be inherently multifunctional and strategies combining radiotherapy and chemotherapy have already been proposed.…”