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

Alison L. Banka, M. Valentina Guevara, Emma R. Brannon, Nhien Q. Nguyen, Shuang Song, Gillian Cady, David J. Pinsky, Kathryn E. Uhrich, Reheman Adili, Michael Holinstat and Omolola Eniola-Adefeso ()
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Alison L. Banka: University of Michigan
M. Valentina Guevara: University of Michigan
Emma R. Brannon: University of Michigan
Nhien Q. Nguyen: University of California Riverside
Shuang Song: University of California Riverside
Gillian Cady: University of Michigan
David J. Pinsky: University of Michigan
Kathryn E. Uhrich: University of California Riverside
Reheman Adili: University of Michigan
Michael Holinstat: University of Michigan
Omolola Eniola-Adefeso: University of Michigan

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-37990-z

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