Long circulating nanoparticles via adhesion on red blood cells: mechanism and extended circulation

Polymeric nanoparticles have long been sought after as carriers for systemic and targeted drug delivery. However, applications of nanoparticles are limited by their short in vivo circulation lifetimes. We report that by attaching polymeric nanoparticles to the surface of red blood cells, it is possible to dramatically improve their in vivo circulation lifetime. The particles remain in circulation as long as they remain attached to red blood cells. Particles eventually detach from red blood cells due to shear forces and cell-cell interactions and are subsequently cleared in the liver and spleen. Circulation of red blood cells themselves is not affected by particle attachment procedures. This manuscript reports an in depth analysis of the behavior of nanoparticles bound to red blood cells, especially their circulation characteristics, biodistribution, and mechanisms of clearance.