Inducible endothelial leakiness in nanotherapeutic applications

All intravenous delivered nanomedicine needs to escape from the blood vessel to exert their therapeutic efficacy at their designated site of action. Failure to do so increases the possibility of detrimental side effects and negates their therapeutic intent. Many powerful anticancer nanomedicine strategies rely solely on the tumor derived enhanced permeability and retention (EPR) effect for the only mode of escaping from the tumor vasculature. However, not all tumors have the EPR effect nor can the EPR effect be induced or controlled for its location and timeliness. In recent years, there have been exciting developments along the lines of inducing endothelial leakiness at the tumor to decrease the dependence of EPR. Physical disruption of the endothelial-endothelial cell junctions with coordinated biological intrinsic pathways have been proposed that includes various modalities like ultrasound, radiotherapy, heat and even nanoparticles, appear to show good progress towards the goal of inducing endothelial leakiness. This review explains the intricate and complex biological background behind the endothelial cells with linkages on how updated reported nanomedicine strategies managed to induce endothelial leakiness. This review will also end off with fresh insights on where the future of inducible endothelial leakiness holds.