(282c) Utilizing Shape for Selective Targeting of Leukocytes

Authors: 
Safari, H., University of Michigan
Saito, E., University of Michigan
Kelley, W., University of Michigan
Shea, L., University of Michigan
Eniola-Adefeso, O., University of Michigan
Carethers, L., University of Michigan
Upon introduction into the bloodstream, micro/nanoparticles are subject to phagocytosis by leukocytes. Particle shape is a recently emerged design parameter for the micro/nanocarriers, which directly affects their immune clearance and phagocytosis. Previous studies have demonstrated that increasing the aspect ratio of particles will reduce their clearance by macrophages, and long enough particles can avoid clearance by macrophages. However, the impact of the aspect ratio of particles on their uptake by neutrophils, which are the most abundant phagocytic immune cells in human blood and first responder in case of an injury and inflammation is not well understood. Herein, we examine that the effect of the shape on phagocytosis is the direct consequence of the phagocyte type. In contrary to the observed trend for macrophages, we found that increasing the aspect ratio of the particle increased their uptake by primary human and mouse neutrophils. The difference between particles of varying aspect ratios becomes most prominent for mid-sized microparticles with an equivalent spherical diameter of 1 µm, and ellipsoidal rods can have up to 4-fold increased uptake by neutrophil compared to spheres of the same volume. The observed difference between the response of various phagocyte groups to aspect ratio can introduce shape as a design parameter to selectively target neutrophils while having minimal effect on other leukocyte groups.