Figure 1.

Systemic barriers to nanoparticle tumor delivery. A) After intravenous administration of nanoparticles, various serum proteins adsorb onto the nanoparticle surface and form a protein corona; among these proteins are opsonins, that trigger nanoparticle phagocytosis by immune cells such as circulating or tissue resident macrophages. B) Off target accumulation of nanoparticles in various organs results in fewer nanoparticles reaching the tumor microenvironment. Typically, the liver, spleen, and lungs sequester a large portion of administered nanoparticles. This accumulation is largely dependent on nanoparticle size and surface chemistry. Due to the filtration limit of kidneys being roughly 6 nm, larger nanoparticles do not greatly accumulate in kidneys, however, the kidneys have a much larger role in the accumulation and elimination of sub-6-nm nanoparticles.