Fig. 1.

Schematic representation of the contact-facilitated drug delivery mechanism. Phospholipid encapsulated PFOB nanoparticle with incorporated homing ligand and fumagillin prodrug intereacts with a target cell via ligand-tethering, leading to the hemifusion of the two lipid membranes. The continuity of the nanoparticle monolayer and the outer leaflet of the target cell permit the transfer of the fumagillin prodrug from the nanoparticle to the inner leaflet of the target cell membrane. Once inside the cell, the prodrug undergoes a regioselective enzymatic cleavage at the Sn 2 site by local phospholipase (such as phospholipase A2, PLA-2) to release the active form of the drug.