Towards convergence of photodynamic (TFD) and photothermal (TFT) therapies on in vitro culture of melanoma-derived cells

Abstract

Cancer is one of the main causes of diseases in the world, being characterized by the uncontrolled growth of the cells. 1 out of 3 types of diagnosticated cancer is from skin, which represents 19.3 million of cases worldwide in 2020. In the search for less invasive clinical treatments, light-based therapies have drawn attention, such as photothermal (PTT) and photodynamic (PDT) therapies. Metallic nanoparticles act as photothermal agents, converting light into heating and triggering cell death via hyperthermia, while photosensitizers (PS) generate reactive oxygen species (ROS) when photoactivated, inducing cell death via oxidative stress. However, the PS are prone to photodegradation, losing efficiency after a period of exposure to light. In contrast, metallic nanoparticles have high absorption efficiency and are free from photodegradation. Thus, the synergy between PTT and PDT has been promising, overcoming the aforementioned deficiencies, and improving the therapeutic efficiency through the dual effect. In this project, gold nanoparticles will be coated with silica (AuSHINs), conjugated with the PS methylene violet 3RAX (MV), followed by a final layer of silica for further functionalization with specific antibodies for the skin cancer. The toxicity and phototoxicity of these nanostructures will be evaluated against the in vitro culture of cells derived from primary (A375) and metastatic (SH-4) melanoma. We shall promote the dual effect of PTT and PDT trough the conjugation and further confer specificity to the tumor cells via antibody functionalization. The final goal will be to evaluate the efficiency of the functionalized nanostructure (TFT + TFD) compared to VM (TFD) and AuSHINs (TFT), in addition to unraveling the mechanisms of cell death triggered by the different nanostructures. This PhD project is inserted in the thematic project of FAPESP 2018/22214-6.