Physiological barriers encountered by NPs. a) Upon injection into the blood, NPs circulate throughout the body reaching the capillaries of the liver, kidneys, tumor, and brain. b) Passive accumulation in the tumor occurs with NPs with hydrodynamic diameters between 30–200 nm. i) endothelial cell, ii) tumor cell. c) The Kupffer cells of the liver readily recognize materials with hydrodynamic diameters larger than 100 nm and removes them from circulation. i) endothelial cell, ii) Kupffer cell, iii) hepatocyte. d) The pores of the glomerulus in the kidneys are around 10 nm and thus materials with hydrodynamic diameters larger than this will avoid renal filtration. i) endothelial cell, ii) glomerular basement membrane. e) The blood-brain barrier (BBB) prevents passive accumulation of materials in the brain due to tight junctions between endothelial cells, and thus active or disruptive mechanisms must be used to bypass the BBB.