Tunable particles alter macrophage uptake based on combinatorial effects of physical properties

The ability to tune phagocytosis of particles by macrophages can enhance macrophage internalization of particulate vaccines, for example, to improve protection. Conversely, this ability can increase targeting to desired, non-phagocytic cell populations by reducing the phagocytic susceptibility of particle-based therapeutics. Since phagocytosis is affected by the physical and chemical properties of particles, it is crucial to identify any interplay between all physical properties of particles in altering phagocytic interactions. To achieve this, a template based layer-by-layer assembly process was used to fabricate tunable particles whose physical properties size, shape and stiffness can be altered while retaining the same surface chemistry. We investigated the combined effect of such physical properties on macrophage interactions in Fc receptor-mediated phagocytosis. Our results highlight how changing particle stiffness works in a complex way on phagocytic interaction when combined with varying size or shape. Increase in size plays a dominant role over reduction in stiffness in reducing internalization by macrophages for a spherical shape. Internalization of rod shaped particles, but not spherical particles, was highly dependent on stiffness. These particles demonstrate the interplay between size, shape and stiffness in tuning the interactions of Fc-functionalized particles with macrophages during phagocytosis. This article is protected by copyright. All rights reserved.