Combination of gold nanoparticles with near-infrared light as an alternative approach for melanoma management
Joana Lopes, Carla Rodrigues, Ana Godinho‐Santos, João M. P. Coelho, Luís C. Cabaço, Duarte C. Barral, Pedro Faísca, José Catarino, Daniela Nunes, Elvira Fortunato, Rodrigo Martins, Cecília M. P. Rodrigues, Maria Manuela Gaspar, Catarina Pinto Reis
Abstract
• Physicochemical, morphological and elemental characterization of gold nanoparticles (AuNPs); • Elucidation of the mechanisms of action of developed AuNPs in combination with laser; • Inductively Coupled Plasma confirmed the retention of AuNPs at tumor site; • AuNPs in combination with laser exhibited antitumor effect in a murine melanoma model; • Photothermal therapy using AuNPs holds a high potential in the treatment of superficial and localized tumors. Melanoma is the most aggressive type of skin cancer and recently approved drugs are often associated with resistance and significant adverse effects. Therefore, the design of more effective and safe options remains imperative. Photothermal therapy (PTT) using gold nanoparticles (AuNPs) presents a promising and innovative approach. In this work, the efficacy of combining a previously optimized formulation of AuNPs coated with a mixture of hyaluronic and oleic acids (HAOA-AuNPs) with near-infrared (NIR) laser irradiation in melanoma cell lines was explored. Coated and uncoated AuNPs formulations were characterized in physicochemical, morphological and elemental terms. Next, the cellular uptake efficiency as well as antiproliferative activity of the combination of each formulation with laser irradiation was evaluated. Subsequently, HAOA-AuNPs were selected to assess the underlying mechanism of combined therapy by cell cycle and Annexin V/PI assays. An in vivo syngeneic murine melanoma model was also conducted. In vitro studies demonstrated that 24 h after incubation and in the absence of laser, HAOA-AuNPs did not exhibit cytotoxic effects on the melanoma cell lines tested, similar to the laser alone. On the contrary, the combination therapy resulted in a large reduction in cell viability. Furthermore, it has been shown to promote S-phase cell cycle arrest and increase in the percentage of late apoptotic cells. Finally, the in vivo proof-of-concept showed that the intratumoral administration of HAOA-AuNPs followed by three laser irradiations impaired tumor progression. Collectively, AuNP-based PTT holds significant potential to improve treatment efficacy and safety, offering a versatile and potent tool against cancer.