Figure 6.

Schematic illustrating critical differences between normal and tumor tissues, lymphatic drainage of small molecules is reduced in tumor tissues, tumor vasculature has different porosity due to defective endothelial cells and pro-angiogenesis, tumors typically have an increased interstitial fluid pressure, and the dense collagen and cellular network forms a physical barrier within the tumor. Physicochemical factors affecting targeting include size, shape, flexibility, and surface properties. (a) Nanoparticles without proper stealthy decoration may be rapidly recognized and cleared through phagocytosis, while anisotropic or flexible nanoparticles are more likely to avoid phagocytosis. (b) Nanoparticles that are too large cannot enter the tumor from the vasculature despite its enhanced permeability. (c) Ligand density, orientation, clustering, and tethers all affect ligand-mediated endocytosis.