In recent years, gold nanoparticles (AuNPs) have aroused the interest of many researchers due to their unique physicochemical and optical properties. AuNPs are being explored in a variety of biomedical fields, either in diagnostics or therapy, particularly for localized thermal ablation of cancer cells after light irradiation. Besides the promising therapeutic potential of AuNPs, their safety constitutes a highly important issue for any medicine or medical device. For this reason, in the present work, the production and characterization of physicochemical properties and morphology of AuNPs coated with two different materials (hyaluronic and oleic acids (HAOA) and bovine serum albumin (BSA)) were firstly performed. Based on the above importantly referred issue, the in vitro safety of developed AuNPs was evaluated in healthy keratinocytes, human melanoma, breast, pancreatic and glioblastoma cancer cells, as well as in a three-dimensional human skin model. Ex vivo and in vivo biosafety assays using, respectively, human red blood cells and Artemia salina were also carried out. HAOA-AuNPs were selected for in vivo acute toxicity and biodistribution studies in healthy Balb/c mice. Histopathological analysis showed no significant signs of toxicity for the tested formulations. Overall, several techniques were developed in order to characterize the AuNPs and evaluate their safety. All these results support their use for biomedical applications.

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.

Breast cancer is a high-burden malignancy for society, whose impact boosts a continuous search for novel diagnostic and therapeutic tools. Among the recent therapeutic approaches, photothermal therapy (PTT), which causes tumor cell death by hyperthermia after being irradiated with a light source, represents a high-potential strategy. Furthermore, the effectiveness of PTT can be improved by combining near infrared (NIR) irradiation with gold nanoparticles (AuNPs) as photothermal enhancers. Herein, an alternative synthetic method using rosmarinic acid (RA) for synthesizing AuNPs is reported. The RA concentration was varied and its impact on the AuNPs physicochemical and optical features was assessed. Results showed that RA concentration plays an active role on AuNPs features, allowing the optimization of mean size and maximum absorbance peak. Moreover, the synthetic method explored here allowed us to obtain negatively charged AuNPs with sizes favoring the local particle accumulation at tumor site and maximum absorbance peaks within the NIR region. In addition, AuNPs were safe both in vitro and in vivo. In conclusion, the synthesized AuNPs present favorable properties to be applied as part of a PTT system combining AuNPs with a NIR laser for the treatment of breast cancer.

The Antarctic toothfish Dissostichus mawsoni is a Southern Ocean long-lived top predator which is regularly captured on an annual fishery operating in the region. By its biological and ecological characteristics, it is a potential bioindicator for the concentrations of trace and rare earth elements in the Antarctic. As these elements are mainly transferred through the diet and a deficiency or excess of these elements can lead to diverse health problems, it is important to measure their concentrations on the organisms. This study provides, for the first time, the concentration of 27 trace (major essential, minor essential and non-essential) and rare earth elements in the muscle of D. mawsoni captured in three areas of the Amundsen and Dumont D'Urville Seas (Antarctica). Major essential elements had the highest concentrations, with potassium (K) as the most concentrated, and rare earth elements the lowest. Significant differences between areas were found for most of the studied elements. No bioaccumulation nor biomagnification potential was found for the studied elements, with several elements decreasing concentrations towards larger individuals. Decreasing trends are related with the different habitats occupied by D. mawsoni through their life, suggesting that elements' concentrations in the water is determinant for the concentrations in this top predator, and/or there is a dilution effect as the fish grows. Our results also support that Se presents a detoxification potential for Hg in D. mawsoni, but only when Hg concentrations are higher to unhealthy levels. This study supports D. mawsoni as a potential bioindicator for the concentrations of the different trace and rare earth elements in the Southern Ocean, though only when comparing individuals of similar size/age, but also to evaluate annual changes on their concentrations. Furthermore, D. mawsoni can be a good source of major essential elements to humans with concentrations of major essential elements above some of other marine fish worldwide.