LAUSR

Simple Summary Anaplastic thyroid carcinoma (ATC) is a subtype of thyroid cancer that generally does not respond to the available treatments, making it one of the most lethal cancers known. As an alternative, Photothermal Therapy (PTT) can be considered a promising strategy. In this case, gold nanoparticles (AuNPs) are activated when irradiated by light, enhancing the local temperature, resulting in cell death. Thus, this study aims to formulate AuNPs specifically for targeting PTT to ATC. For this, biocompatible AuNPs were designed and functionalized with ATC-specific ligands (holo-transferrin, epidermal growth factor (EGF), and lapatinib), showing optimal physicochemical properties. Safety, efficacy, and ATC specificity were determined in vitro. Holo-transferrin functionalized-AuNPs were the most effective for PTT against ATC. Safety and biodistribution were studied in vivo, proving that the formulation was safe for intratumoural administration. So, taking these results all together, AuNPs-mediated-PTT seems to be a promising hint to find a viable treatment for ATC. Abstract Anaplastic thyroid carcinoma (ATC) is a very rare subtype of thyroid carcinoma and one of the most lethal malignancies. Poor prognosis is mainly associated with its undifferentiated nature, inoperability, and failing to respond to the typically used therapies for thyroid cancer. Photothermal Therapy (PTT) entails using light to increase tissues’ temperature, leading to hyperthermia-mediated cell death. Tumours are more susceptible to heat as they are unable to dissipate it. By using functionalized gold nanoparticles (AuNPs) that transform light energy into heat, it is possible to target the heat to the tumour. This study aims to formulate ATC-targeted AuNPs able to convert near-infrared light into heat, for PTT of ATC. Different AuNPs were synthetized and coated. Size, morphology, and surface plasmon resonances band were determined. The optimized coated-AuNPs were then functionalized with ligands to assess ATC’s specificity. Safety, efficacy, and selectivity were assessed in vitro. The formulations were deemed safe when not irradiated (>70% cell viability) and selective for ATC. However, when irradiated, holo-transferrin-AuNPs were the most cytotoxic (22% of cell viability). The biodistribution and safety of this formulation was assessed in vivo. Overall, this novel formulation appears to be a highly promising approach to evaluate in a very near future.