Cargo-free particles divert neutrophil-platelet aggregates to reduce thromboinflammation

Platelet-neutrophil aggregates are a hallmark of thromboinflamation. Here, the authors use cargo-free particles to block platelet-neutrophil aggregates' vascular wall adhesion, which could become an effective thromboinflammation therapy, regardless of disease cause. The combination of inflammation and thrombosis is a hallmark of many cardiovascular diseases. Under such conditions, platelets are recruited to an area of inflammation by forming platelet-leukocyte aggregates via interaction of PSGL-1 on leukocytes and P-selectin on activated platelets, which can bind to the endothelium. While particulate drug carriers have been utilized to passively redirect leukocytes from areas of inflammation, the downstream impact of these carriers on platelet accumulation in thromboinflammatory conditions has yet to be studied. Here, we explore the ability of polymeric particles to divert platelets away from inflamed blood vessels both in vitro and in vivo. We find that untargeted and targeted micron-sized polymeric particles can successfully reduce platelet adhesion to an inflamed endothelial monolayer in vitro in blood flow systems and in vivo in a lipopolysaccharide-induced, systemic inflammation murine model. Our data represent initial work in developing cargo-free, anti-platelet therapeutics specifically for conditions of thromboinflammation.

Automated summary

The authors used cargo-free particles to block the adhesion of platelet-neutrophil aggregates to the vascular wall, potentially providing an effective therapy for thromboinflammation. Platelets are recruited to areas of inflammation through the interaction of PSGL-1 on leukocytes and P-selectin on activated platelets, leading to platelet-leukocyte aggregates that bind to the endothelium. In this study, polymeric particles were found to divert platelets away from inflamed blood vessels both in vitro and in vivo, suggesting their potential as anti-platelet therapeutics for thromboinflammatory conditions.