ACS Nano http://doi.org/p42 (2013)

The rapid removal of foreign materials by mononuclear phagocytic systems that are located in the spleen and liver limit the ability of nanoparticles to exert their potentially therapeutic effect. One way pathogens can circulate inside the body is by using red blood cells as carriers, an approach known as cellular hitchhiking. The advantage of using red blood cells is that they naturally avoid clearance by mononuclear phagocytic systems. Samir Mitragotri and colleagues at the University of California, Santa Barbara and the University of Pennsylvania have now shown that this strategy can be applied to nanoparticles to increase both their accumulation in body tissues and circulation time.

The researchers incubated polystyrene nanoparticles with red blood cells, injected samples into the tail vein of mice, and observed a marked change in the behaviour of the nanoparticles, compared with free nanoparticles. They detected a seven-fold increase in the accumulation of red blood cell adsorbed-nanoparticles in the lungs and suggest that the nanoparticles are dislodged from the blood cells when being squeezed through the tiny capillaries of the lung vasculature, allowing accumulation in the tissue; the blood cells are able to continue functioning and circulating around the body. Attachment to the blood cells also reduced accumulation in the spleen and liver.

The team improved on this by modifying the surface of the nanoparticle with anti-ICAM-1, an antibody that can attach to endothelial cells in the lung. This extended the retention of the blood cell adsorbed-nanoparticles in the lungs from 10 hours to over 24 hours.