Metastatic melanoma represents one of the most aggressive forms of skin cancer, characterized by high invasive potential and profound alterations within the tumor microenvironment. A crucial role in this process is played by the silencing of tissue inhibitor of metalloproteinases-3 (TIMP-3), a tumor suppressor protein that regulates extracellular matrix remodeling, angiogenesis, and apoptosis. This thesis focused on the development and characterization of an innovative local delivery system, based on the integration of polymeric nanoparticles into a thermoresponsive hydrogel, for the delivery of TIMP-3 mRNA. The methodology involved the synthesis of poly(beta-amino ester) (pBAE) nanoparticles (NPs) modified with oligopeptides (lysine and histidine), optimized for mRNA encapsulation.