Transvascular drug delivery in solid tumors

The microvessel wall is a barrier for the delivery of various therapeutic agents to tumor cells. Tumor microvessels are, in general, more permeable to macromolecules than normal vessels. The hyperpermeability is presumably due to the existence of large pore structures in the vessel wall, induced by various cytokines. The cutoff pore size is tumor dependent, as determined by transport studies of nanoparticles. The vascular permeability is heterogeneous in tumors and dependent on physicochemical properties of molecules as well as the ultrastructure of the vessel wall. The ultrastructure is dynamic and can be modulated by the tumor microenvironment. The microenvironment itself can be altered by the transvascular transport because the transport may facilitate angiogenesis, reduce blood flow, and induce interstitial hypertension in tumors. Future studies of transport need to address mechanisms of the barrier formation and emphasize development of novel strategies for circumventing or exploiting the vascular barrier.