Rod‐shaped Polymerized Salicylic Acid Particles Modulate Neutrophil Transendothelial Migration in Acute Inflammation

Rod-shaped particles outperform spherical particles of the same volume in preventing neutrophil infiltration to inflamed areas, both in vitro and in vivo. This therapeutic effectiveness is attributed to better cell targeting and decreased cell motility, resulting from the geometry-driven phagocytosis and inhibited actin polymerization.

Abstract

Neutrophilic inflammation is present in numerous high-mortality pathologies, including sepsis, deep vein thrombosis, and acute lung injury (ALI). Therefore, regulating neutrophil recruitment becomes an attractive therapeutic approach for neutrophil-mediated inflammation. Here, the impact of salicylic acid-based polymeric particles in regulating neutrophil recruitment in vivo and in vitro, particularly investigating the impact of neutrophil targeting via particle geometry-driven phagocytosis is explored. It is found that rod-shaped polymeric particles can improve neutrophil targeting in a murine ALI model, effectively preventing neutrophil infiltration into the mice's lungs compared to spherical particles of the same volume. It is demonstrated that the elongated nature of the polymeric carriers reduced neutrophils’ transmigration ability across endothelial barriers in vivo and in vitro, contributing to their therapeutic effectiveness. These data represent initial work in developing non-spherical particle-mediated targeting of activated neutrophils for conditions affected by neutrophilic injury.