Figure 4.

Passive and active targeting of nanocarriers within melanoma TME. Under certain conditions (e.g., hypoxia and inflammation) different factors (bradykinin, nitric oxide, prostaglandins, VEGF, cytokines) induce an increased permeability of the endothelium of tumor blood vessels. The rapidly growing tumor is facilitated by new vessels formation that contribute to the permeation of nanocarriers to the tumor stroma. Furthermore, the absence of normal lymphatic drainage in tumors contribute to the nanocarriers retention (EPR effect). In these conditions, the passive uptake of nanocarriers is improved (passive targeting). On the contrary, the decoration of the nanocarrier surfaces with ligands that recognize the tumor cell receptors facilitates the drugs delivery in melanoma TME.