A model of modified meta-iodobenzylguanidine conjugated gold nanoparticles for neuroblastoma treatment

Abstract

Iodine-131 meta-iodobenzylguanidine (¹³¹I-mIBG) has been utilized as a standard treatment to minimize adverse side effects by targeting therapies to bind to the norepinephrine transporter (NET) expressed on 90% of neuroblastoma cells. However, only a minority of patients who receive ¹³¹I-mIBG radiotherapy have clinical responses, and these are usually not curative. In this study, novel ligand-conjugated gold nanoparticles (GNPs) based on mIBG were synthesized and evaluated biologically with neuroblastoma cells in vitro. To induce specific internalization to the tumor cells and utilize it as a model for radioenhancement, ¹²⁷I-modified mIBG was successfully synthesized and grafted covalently to the surface of carboxylated PEG-GNPs. 49.28% of the novel mIBG derivative was grafted on carboxylated PEG-GNPs. The particles were stable and not toxic to the normal fibroblast cell line, L929, even at the highest concentration tested (10¹³ NPs per mL) at 24, 48, and 72 h. Moreover, the cellular uptake of the model was decreased significantly in the presence of a NET inhibitor, suggesting that there was specific internalization into neuroblastoma cells line (SH-SY5Y) via the NET. Therefore, this model provides useful guidance toward the design of gold nanomaterials to enhance the efficiency of ¹³¹I-mIBG treatment in neuroblastoma patients. However, the investigation of radio-therapeutic efficiency after radioisotope ¹³¹I substitution will be further conducted in a radiation safety laboratory using an animal model.