Rational approach to design gold nanoparticles for photothermal therapy: the effect of gold salt on physicochemical, optical and biological properties.

Among the unique characteristics associated to gold nanoparticles (AuNPs) in biomedicine, their ability to convert light energy into heat opens ventures for improved cancer therapeutic options, such as photothermal therapy (PTT). PTT relies on the local hyperthermia of tumor cells upon irradiation with light beams, and the association of AuNPs with radiation within the near infrared (NIR) range constitutes an advantageous strategy to potentially improve PTT efficacy. Herein, it was explored the effect of the gold salt on the AuNPs' physicochemical and optical properties. Mostly spherical-like negatively charged AuNPs with variable sizes and absorbance spectra were obtained. In addition, photothermal features were assessed using in vitro phantom models. The best formulation showed the ability to increase their temperature in aqueous solution up to 19 °C when irradiated with a NIR laser for 20 min. Moreover, scanning transmission electron microscopy confirmed the rearrangement of the gold atoms in a face-centered cubic structure, which further allowed to calculate the photothermal conversion efficiency upon combination of theoretical and experimental data. AuNPs also showed local retention after being locally administered in in vivo models. These last results obtained by computerized tomography allow to consider these AuNPs as promising elements for a PTT system. Moreover, AuNPs showed high potential for PTT by resulting in in vitro cancer cells' viability reductions superior to 70 % once combine with 5 min of NIR irradiation.

Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma.

The global impact of cancer emphasizes the importance of developing innovative, effective and minimally invasive therapies. In the context of superficial cancers, the development of a multifunctional nanoparticle-based system and its in vitro and in vivo safety and efficacy characterization are, herein, proposed as a proof-of-concept. This multifunctional system consists of gold nanoparticles coated with hyaluronic and oleic acids, and functionalized with epidermal growth factor for greater specificity towards cutaneous melanoma cells. This nanoparticle system is activated by a near-infrared laser. The characterization of this nanoparticle system included several phases, with in vitro assays being firstly performed to assess the safety of gold nanoparticles without laser irradiation. Then, hairless immunocompromised mice were selected for a xenograft model upon inoculation of A375 human melanoma cells. Treatment with near-infrared laser irradiation for five minutes combined with in situ administration of the nanoparticles showed a tumor volume reduction of approximately 80% and, in some cases, led to the formation of several necrotic foci, observed histologically. No significant skin erythema at the irradiation zone was verified, nor other harmful effects on the excised organs. In conclusion, these assays suggest that this system is safe and shows promising results for the treatment of superficial melanoma.

Calcitriol loading before total parathyroidectomy with autotransplant in patients with end-stage kidney disease: does it prevent postoperative hypocalcaemia?

BACKGROUND: Hungry bone syndrome (HBS) is one of the most serious complications following parathyroidectomy for severe hyperparathyroidism. There is a lack of literature informing the treatment and risk factors for this condition and the ideal pre-operative strategy for prevention. AIMS: The primary aims were to examine the incidence of HBS with pre-operative calcitriol loading for 10 days and to determine the risk factors for HBS. The secondary aims were to determine the rate of intravenous calcium replacement in those with HBS and to assess whether cinacalcet removal has increased rates of parathyroidectomy in the end-stage kidney disease population. METHODS: We performed a retrospective study from 2011 to 2018 on 45 patients with end-stage kidney disease undergoing total parathyroidectomy with autotransplantation for severe hyperparathyroidism. This was based at the John Hunter and Newcastle Private Hospitals in New South Wales. RESULTS: 28.3% of patients with calcitriol loading undergoing parathyroidectomy fulfilled criteria for HBS. Pre-operative variables that were associated with HBS were elevated parathyroid hormone (P = 0.028) and longer duration of renal replacement therapy (P = 0.033). Rates of total parathyroidectomy were higher after the removal of calcimimetics from the Pharmaceutical Benefits Scheme (P = 0.0024). CONCLUSIONS: HBS remains a common complication of parathyroidectomy, even with prolonged high-dose calcitriol loading. This emphasises the need for further trials investigating other targeted therapies, such as bisphosphonates, to prevent HBS. Those most at risk of HBS are patients with high bone turnover and prolonged renal replacement therapy.