RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept
Presently, a new era of drug-eluting stents is continuing to improve late adverse effects such as thrombosis after coronary stent implantation in atherosclerotic vessels. The application of gene expression–modulating stents releasing specific small interfering RNAs (siRNAs) or messenger RNAs (mRNAs)...
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doaj-239060b310d8499897d444e8287749af2020-11-25T03:59:16ZengMDPI AGPharmaceuticals1424-82472017-02-011012310.3390/ph10010023ph10010023RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent ConceptOlivia Koenig0Diane Zengerle1Nadja Perle2Susanne Hossfeld3Bernd Neumann4Andreas Behring5Meltem Avci-Adali6Tobias Walker7Christian Schlensak8Hans Peter Wendel9Andrea Nolte10Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyDepartment of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, GermanyPresently, a new era of drug-eluting stents is continuing to improve late adverse effects such as thrombosis after coronary stent implantation in atherosclerotic vessels. The application of gene expression–modulating stents releasing specific small interfering RNAs (siRNAs) or messenger RNAs (mRNAs) to the vascular wall might have the potential to improve the regeneration of the vessel wall and to inhibit adverse effects as a new promising therapeutic strategy. Different poly (lactic-co-glycolic acid) (PLGA) resomers for their ability as an siRNA delivery carrier against intercellular adhesion molecule (ICAM)-1 with a depot effect were tested. Biodegradability, hemocompatibility, and high cell viability were found in all PLGAs. We generated PLGA coatings with incorporated siRNA that were able to transfect EA.hy926 and human vascular endothelial cells. Transfected EA.hy926 showed significant siICAM-1 knockdown. Furthermore, co-transfection of siRNA and enhanced green fluorescent protein (eGFP) mRNA led to the expression of eGFP as well as to the siRNA transfection. Using our PLGA and siRNA multilayers, we reached high transfection efficiencies in EA.hy926 cells until day six and long-lasting transfection until day 20. Our results indicate that siRNA and mRNA nanoparticles incorporated in PLGA films have the potential for the modulation of gene expression after stent implantation to achieve accelerated regeneration of endothelial cells and to reduce the risk of restenosis.http://www.mdpi.com/1424-8247/10/1/23atherosclerosisdrug eluting stentsPLGA filmsgene deliverylocal transfectionsiICAM-1gene knockdownmRNA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Olivia Koenig Diane Zengerle Nadja Perle Susanne Hossfeld Bernd Neumann Andreas Behring Meltem Avci-Adali Tobias Walker Christian Schlensak Hans Peter Wendel Andrea Nolte |
spellingShingle |
Olivia Koenig Diane Zengerle Nadja Perle Susanne Hossfeld Bernd Neumann Andreas Behring Meltem Avci-Adali Tobias Walker Christian Schlensak Hans Peter Wendel Andrea Nolte RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept Pharmaceuticals atherosclerosis drug eluting stents PLGA films gene delivery local transfection siICAM-1 gene knockdown mRNA |
author_facet |
Olivia Koenig Diane Zengerle Nadja Perle Susanne Hossfeld Bernd Neumann Andreas Behring Meltem Avci-Adali Tobias Walker Christian Schlensak Hans Peter Wendel Andrea Nolte |
author_sort |
Olivia Koenig |
title |
RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept |
title_short |
RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept |
title_full |
RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept |
title_fullStr |
RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept |
title_full_unstemmed |
RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept |
title_sort |
rna-eluting surfaces for the modulation of gene expression as a novel stent concept |
publisher |
MDPI AG |
series |
Pharmaceuticals |
issn |
1424-8247 |
publishDate |
2017-02-01 |
description |
Presently, a new era of drug-eluting stents is continuing to improve late adverse effects such as thrombosis after coronary stent implantation in atherosclerotic vessels. The application of gene expression–modulating stents releasing specific small interfering RNAs (siRNAs) or messenger RNAs (mRNAs) to the vascular wall might have the potential to improve the regeneration of the vessel wall and to inhibit adverse effects as a new promising therapeutic strategy. Different poly (lactic-co-glycolic acid) (PLGA) resomers for their ability as an siRNA delivery carrier against intercellular adhesion molecule (ICAM)-1 with a depot effect were tested. Biodegradability, hemocompatibility, and high cell viability were found in all PLGAs. We generated PLGA coatings with incorporated siRNA that were able to transfect EA.hy926 and human vascular endothelial cells. Transfected EA.hy926 showed significant siICAM-1 knockdown. Furthermore, co-transfection of siRNA and enhanced green fluorescent protein (eGFP) mRNA led to the expression of eGFP as well as to the siRNA transfection. Using our PLGA and siRNA multilayers, we reached high transfection efficiencies in EA.hy926 cells until day six and long-lasting transfection until day 20. Our results indicate that siRNA and mRNA nanoparticles incorporated in PLGA films have the potential for the modulation of gene expression after stent implantation to achieve accelerated regeneration of endothelial cells and to reduce the risk of restenosis. |
topic |
atherosclerosis drug eluting stents PLGA films gene delivery local transfection siICAM-1 gene knockdown mRNA |
url |
http://www.mdpi.com/1424-8247/10/1/23 |
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