Figure 4.

The impact of pharmaceutical vessel modulation on macro- and microtumor vasculature and on tumor-targeted drug delivery. During vessel permeabilization, the gaps between the endothelial cells are widened due the vasodilatation and increased gaps between endothelial and perivascular cells. Vessel normalization restores the morphology and functionality of the tumor vasculature by improving vascular perfusion and promoting vascular maturity. Vascular disruption tampers with the endothelial lining and reduces the perfusion (of immature vasculature), which enhances the vascular permeability. Vascular promotion increases vessel density and distribution leading to an enhanced relative blood volume in tumors. On the basis of the vascular characteristics of tumors, many pharmaceutical strategies could be used that have different effects on the penetration and accumulation of the drugs and drug delivery systems. Reproduced with permission from ref (36). Copyright 2017 Elsevier Publishing.