(567d) Cargo-Free Particles Effectively Divert Neutrophil-Platelet Aggregates to Reduce Thromboinflammation

The combination of inflammation and thrombosis is characteristic of many diseases, including ischemic stroke, atherosclerosis, deep vein thrombosis, and myocardial infarction. Platelets are essential in maintaining hemostasis to prevent extreme blood loss and permanent injuries. Platelets' close interaction with the inflamed endothelium and their contribution to intravascular thrombi formation (or blood clot) can often exacerbate thromboinflammatory pathologies. Leukocytes, particularly neutrophils, also contribute to thrombus development by forming aggregates with platelets. During thromboinflammation, neutrophils-platelet aggregates are formed via the interaction of PSGL-1 on leukocytes and P-selectin on activated platelets, which can together bind and accumulate at the injured endothelium. Particulate drug carriers have been applied to redirect and prevent leukocyte adhesion from areas of injury or inflammation. However, the downstream effect of these particulate carries on neutrophil-platelet and platelet accumulation in thromboinflammatory conditions has yet to be explored. This work investigates the ability of polymeric carriers to divert platelets away from inflamed blood vasculature both in vitro and in vivo. We find that untargeted and targeted micron-sized polymeric particles can successfully decrease platelet adhesion to inflamed endothelial cells in vitro in blood flow assays and in vivo in a murine model of lipopolysaccharide-induced systemic inflammation. Our data represent initial work in creating new, drug-free, anti-platelet therapeutics, particularly for conditions of thromboinflammation.