A signicant increase of reported cutaneous melanoma cases have been observed within the past four decades. Despite numerous therapeutic strategies available and ongoing works on novel therapeutics, the vital prognosis for the diagnosed patients are still poor due to low response rate of the tumors to these treatments. For this reason, the application of interfering RNA (RNAi) as a therapeutic agent allowing reestablishment of physiological process of cellular death seems to be a promising altern ative strategy. The use of nanoparticles enables to i) improve the pharmacokinetic of RNAi, ii) potentialize its efciency and iii) avoid side effects is essential to improve tumor targeting. Therefore, the structure and density of vascularization in a tumor-site is a crucial factor for determining efcacy of nanovectors. This allows the passive targeting which is due to enhanced permeability and retention (EPR) effect. [...]