Anti-Platelet Effect Induced by Iron Oxide Nanoparticles: Correlation with Conformational Change in Fibrinogen |
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Authors: | Regina Komal Kottana Lionel Maurizi Brian Schnoor Kenise Morris Jessica Ann Webb Michael Anthony Massiah Nadine Millot Anne-Laure Papa |
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Affiliation: | 1. Department of Biomedical Engineering, School of Engineering and Applied Science, The George Washington University, Washington, DC, 20052 USA;2. Laboratory ICB, Université Bourgogne Franche-Comté, 9 Avenue Alain Savary, Dijon, F-21078 France;3. Department of Chemistry, Columbian College of Arts and Sciences, The George Washington University, Washington, DC, 20052 USA |
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Abstract: | Iron oxide nanoparticles are developed for various biomedical applications, however, there is limited understanding regarding their effects and toxicity on blood components. The particles traveling in circulation inevitably interact with blood cells and plasma proteins and may interfere with hemostasis. Specifically, this study focuses on the influence of superparamagnetic iron oxide nanoparticles (SPIONs) coated with a biocompatible polymer, polyvinyl alcohol (PVA), on platelet function. Here, engineered SPIONs that are functionalized with various PVA coatings to provide these particles with different surface charges and polymer packing are described. These formulations are assessed for any interference with human platelet functions and coagulation, ex vivo. Positively charged SPIONs induce a significant change in platelet GPIIb-IIIa conformation, indicative of platelet activation at the dose of 500 µg mL−1. Remarkably, engineered PVA(polyvinyl alcohol)-SPIONs all display a robust dose-dependent anti-platelet effect on platelet aggregation, regardless of the PVA charge and molecular weight. After assessing hypotheses involving SPION-induced steric hindrance in platelet–platelet bridging, as well as protein corona involvement in the antiplatelet effect, the study concludes that the presence of PVA-SPIONs induces fibrinogen conformational change, which correlates with the observed dose-dependent anti-platelet effect. |
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Keywords: | anti-platelet effect nanoparticle–protein interactions platelets polyvinyl alcohol superparamagnetic iron oxide nanoparticles |
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