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Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744670/
https://www.ncbi.nlm.nih.gov/pubmed/35008437
http://dx.doi.org/10.3390/ijms23010011
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author 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
author_facet 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
author_sort Nestele, Jeremy A.
collection PubMed
description 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.
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spelling pubmed-87446702022-01-11 Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation 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 Int J Mol Sci Article 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. MDPI 2021-12-21 /pmc/articles/PMC8744670/ /pubmed/35008437 http://dx.doi.org/10.3390/ijms23010011 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation
title Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation
title_full Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation
title_fullStr Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation
title_full_unstemmed Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation
title_short Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation
title_sort characterization of gpvi- or gpvi-cd39-coated nanoparticles and their impact on in vitro thrombus formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744670/
https://www.ncbi.nlm.nih.gov/pubmed/35008437
http://dx.doi.org/10.3390/ijms23010011
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