RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept
| Autor: | Christian Schlensak, Meltem Avci-Adali, Tobias Walker, Bernd Neumann, Diane Zengerle, Nadja Perle, Andreas Behring, Hans Peter Wendel, Andrea Nolte, Olivia Koenig, Susanne Hossfeld |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Small interfering RNA mRNA lcsh:Medicine lcsh:RS1-441 Pharmaceutical Science 030204 cardiovascular system & hematology Gene delivery atherosclerosis drug eluting stents PLGA films gene delivery local transfection siICAM-1 gene knockdown Article lcsh:Pharmacy and materia medica 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Restenosis Drug Discovery Gene expression medicine Gene knockdown Chemistry lcsh:R Transfection medicine.disease Intercellular adhesion molecule Molecular biology Cell biology PLGA 030104 developmental biology Molecular Medicine |
| Zdroj: | Pharmaceuticals Pharmaceuticals; Volume 10; Issue 1; Pages: 23 Pharmaceuticals, Vol 10, Iss 1, p 23 (2017) |
| ISSN: | 1424-8247 |
| DOI: | 10.3390/ph10010023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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