Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes

Polymeric nanoparticles have been extensively studied for use as intravascular drug delivery vehicles; however, their applications are limited by rapid clearance from circulation by the reticuloendothelial system (RES). Previous attempts to improve vascular circulation have focused on surface modification using polymers such as poloxamines, poloxamers, and polyethylene glycol, to prevent opsononization. We report on a novel method of prolonging intravascular particle circulation by anchoring the nanoparticles to the surface of red blood cells (RBCs). We hypothesize that particles adhered to RBCs can escape RES clearance due to the ability of RBCs to do so. This method is motivated by the strategy adopted by certain bacteria, for example, hemobartonella, that adhere to RBCs and remain in circulation for several weeks. Prolonged circulation of nanoparticles as large as 450 nm was observed after adsorption on RBCs. Although particles were eventually eliminated from circulation, RBCs were not cleared. RBC-anchored nanoparticles offer a novel approach for intravascular drug delivery and blood pool imaging.