Ligand-functionalized nanoparticles for targeted therapy of melanoma in situ

Abstract

Cutaneous melanoma occurs on the skin and is the most common type of melanoma. Treatment of cutaneous melanoma has improved over the last thirty years; however, without demonstrating a significant increase on survival of patients with advanced disease. Indeed, conventional treatment generally shows several limitations, such as reduced target specificity, severe adverse effects and multiple drug resistance. In fact, an important step for the success of melanoma treatment is its early detection. In cases where there are no metastases, this cancer can be removed by surgery, but in some cases the risk of intervention has to be measured, as well as the high risk of recurrence, which impose the use of an adjuvant treatment. Currently, there is only one adjuvant treatment approved, with interferon alpha, in these cases. Therefore, the main objective of this thesis was the study of alternatives as adjuvant treatments, more efficient and less aggressive, for cutaneous melanoma. In this context, two strategies have been studied for application of nanoparticles systems. The first strategy is focused on the development of gold nanoparticles, coated with natural polymers and peptides, with absorption at the near infrared range, for photothermal therapy. The second strategy includes the development of hybrid nanoparticles, for encapsulation of anti-tumor compounds, coated with natural polymers and peptides, capable of a local chemotherapy at the tumor site. Overall, the physico-chemical behavior and stability of both nanoparticles for each application were investigated. Recognizing the importance of an efficient and specific treatment, both strategies were based on a specific targeting to melanoma cells, which overexpressed multiple receptors at their surface. At last, animal models for human melanoma were used for evaluation of the efficiency of both proposed strategies. In conclusion, it is possible to develop nanosystems comprising different therapeutic strategies, based on distinct core structures and surface functionalization with multiple targeting ligands, for a broad and potential application in heterogeneous cancers, such as cutaneous melanoma.