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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Main Authors: Olivia Koenig, Diane Zengerle, Nadja Perle, Susanne Hossfeld, Bernd Neumann, Andreas Behring, Meltem Avci-Adali, Tobias Walker, Christian Schlensak, Hans Peter Wendel, Andrea Nolte
Format: Article
Language:English
Published: MDPI AG 2017-02-01
Series:Pharmaceuticals
Subjects:
Online Access:http://www.mdpi.com/1424-8247/10/1/23
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spelling 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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