Deciphering neutrophil dynamics: Enhanced phagocytosis of elastic particles and impact on vascular-targeted carrier performance

Particle elasticity has widely been established to substantially influence immune cell clearance and circulation time of vascular-targeted carriers (VTCs). However, prior studies have primarily investigated interactions with macrophages, monocytic cell lines, and in vivo murine models. Interactions between particles and human neutrophils remain largely unexplored, although they represent a critical aspect of VTC performance. Here, we explore the impact of particle elasticity on primary human neutrophil phagocytosis using polyethylene glycol–based particles of different elastic moduli. We found that neutrophils effectively phagocytose deformable particles irrespective of their modulus, indicating a departure from established phagocytosis trends seen with other types of immune cells. These findings highlight the observed phenotypic difference between different types of phagocytes and underscore the need to characterize VTC performance using various cell types and animal models that represent human systems closely.