(682a) Elongated Particles are Preferentially Phagocytosed by Neutrophils- Opportunity for Selective Targeting of Leukocytes in Acute Inflammation

Recent studies have shown that polymeric particles can be used to modulate the behavior of immune cells for the treatment of various inflammatory conditions. However, the impact of physical design parameters on the interaction of particles with different leukocyte subtypes remains unclear. Particle shape is shown to be a crucial factor in the phagocytosis of polymeric particles by macrophages. Elongated particles are reported to experience reduced uptake by macrophages, which leads to an increased circulation time in blood. However, the impact of shape on the interaction of particles with circulating blood leukocytes remains unclear. Neutrophils are the most abundant leukocyte in human blood and the first responders in the case of injury and inflammation. Thus, it is crucial to study the impact of shape on the phagocytosis of particles by neutrophils. In this work, we investigated the phagocytosis of rod-shaped polymeric particles by human neutrophils relative to other leukocytes. Contrary to macrophages and other mononuclear phagocytes, neutrophils were found to exhibit increased internalization of rods in ex vivo and in vivo experimentation. In whole blood samples, rods were shown to have up to 7-fold increased association with neutrophils compared to monocytes. These results demonstrate that altering the shape of particles can be used to selectively target neutrophils in inflammatory pathologies where they are the key controllers of the disorder.