Figure 5.

Nanoparticle size, shape and surface charge dictate biodistribution among the different organs including the lungs, liver, spleen and kidneys. (a) Spherical particles, including gold nanoparticles, liposomes and polymeric micelles/nanoparticles can vary in size and display disparate in vivo fates. Large rigid particles with diameters >2,000 nm accumulate readily within the spleen and liver, as well as in the capillaries of the lungs. Nanoparticles in the range of 100–200 nm have been shown to extravasate through vascular fenestrations of tumors (the EPR effect) and escape filtration by liver and spleen. As size increases beyond 150 nm, more and more nanoparticles are entrapped within the liver and spleen. Small-sized nanoparticles (<5 nm) are filtered out by the kidneys⁹¹. (b) Novel ‘top-down’ and ‘bottom up’ fabrication techniques have enabled the exploration of different geometries of nanoparticles, including cylindrical and discoidal shapes, which have been shown to exhibit pronounced effects on pharmacokinetics and biodistribution. Different nanoparticle shapes exhibit unique flow characteristics that substantially alter circulating lifetimes, cell membrane interactions and macrophage uptake, which in turn affect biodistribution among the different organs⁹². (c) Charge of nanoparticles stemming from distinct surface chemistries influences opsonization, circulation times and interaction with resident macrophages of organs comprising the MPS, with positively charged particles more prone to sequestration by macrophages in the lungs, liver and spleen. Neutral and slightly negatively charged nanoparticles have longer circulation lifetimes and less accumulation in the aforementioned organs of the MPS⁹³. In both b and c, the size of the nanoparticles is assumed to range from 20–150 nm. Individual panels represent in vivo fates of nanoparticles, taking into account singular design parameters of size, shape and surface charge independent of one another, and for this reason, respective scales vary from one panel to the next. It is important to note that in vivo biodistribution will undoubtedly vary based on the interplay of several of the above parameters.