(A) Passive targeting. Healthy blood vessels are regular and continuous with tight endothelial junctions between cells. Conversely, the angiogenic vessels show gross architectural changes, such as large intracellular pore, presence of interrupted endothelium and incomplete basement membrane, allowing the extravasation of nanoparticles from blood vessels. In the tumour stroma nanoparticles remain trapped due to higher interstitial pressure, due to a lack of effective lymphatic drainage coupled with lower intravascular pressure. These pathophysiological characteristics enhance the tumour site accumulation of nanoparticles. However, aside to the well perfused and rapidly growing regions, a non-uniform tissue oxygenation due to the vascular heterogeneity led to the presence of poorly perfused, often necrotic areas in which the efficacy of the treatment is hampered. (B) Active targeting. In order to improve the intracellular delivery of the drug, nanoparticles could be functionalized with specific ligands that specifically bind receptors expressed primarily on malignant cells leading to receptor-mediated internalization, which is often necessary to release drugs inside the cells.