Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation
| Autor: | Nestele, Jeremy A., Rohlfing, Anne-Katrin, Dicenta, Valerie, Bild, Alexander, Eißler, Daniela, Emschermann, Frederic, Kremser, Marcel, Krutzke, Konstantin, Schäffer, Tilman E., Borst, Oliver, Levi, Moran, Korin, Netanel, Gawaz, Meinrad Paul |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Platelet Aggregation
QH301-705.5 Recombinant Fusion Proteins Apyrase antithrombotic therapy Platelet Membrane Glycoproteins In Vitro Techniques Flow Cytometry Models Biological Article Immunoglobulin Fc Fragments Microscopy Electron Chemistry Fibrinolytic Agents Polylactic Acid-Polyglycolic Acid Copolymer Antigens CD platelets hemostasis Humans nanoparticles Particle Size Biology (General) QD1-999 |
| Zdroj: | International Journal of Molecular Sciences, Vol 23, Iss 11, p 11 (2022) International Journal of Molecular Sciences |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Traditional antithrombotic agents commonly share a therapy-limiting side effect, as they increase the overall systemic bleeding risk. A novel approach for targeted antithrombotic therapy is nanoparticles. In other therapeutic fields, nanoparticles have enabled site-specific delivery with low levels of toxicity and side effects. Here, we paired nanotechnology with an established dimeric glycoprotein VI-Fc (GPVI-Fc) and a GPVI-CD39 fusion protein, thereby combining site-specific delivery and new antithrombotic drugs. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles, NP-BSA, NP-GPVI and NP-GPVI-CD39 were characterized through electron microscopy, atomic force measurements and flow cytometry. Light transmission aggregometry enabled analysis of platelet aggregation. Thrombus formation was observed through flow chamber experiments. NP-GPVI and NP-GPVI-CD39 displayed a characteristic surface coating pattern. Fluorescence properties were identical amongst all samples. NP-GPVI and NP-GPVI-CD39 significantly impaired platelet aggregation. Thrombus formation was significantly impaired by NP-GPVI and was particularly impaired by NP-GPVI-CD39. The receptor-coated nanoparticles NP-GPVI and the bifunctional molecule NP-GPVI-CD39 demonstrated significant inhibition of in vitro thrombus formation. Consequently, the nanoparticle-mediated antithrombotic effect of GPVI-Fc, as well as GPVI-CD39, and an additive impact of CD39 was confirmed. In conclusion, NP-GPVI and NP-GPVI-CD39 may serve as a promising foundation for a novel therapeutic approach regarding targeted antithrombotic therapy. |
| Databáze: | OpenAIRE |
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