Abstract
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.
Highlights
In 2012 more than 17.5 million people died from cardiovascular diseases (CVD), representing 31% of all global deaths
Our results indicate that small interfering RNAs (siRNAs) and messenger RNAs (mRNAs) 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
All three PLGA resomers were non-toxic to EA.hy926 cells and proved hemocompatible with no adherence of blood cells on the PLGA coatings, a crucial point with respect to preventing thrombosis after stent implantation
Summary
In 2012 more than 17.5 million people died from cardiovascular diseases (CVD), representing 31% of all global deaths. New drug-coated stents rely on the capture of endothelial progenitor cells with specific antibodies such as anti-CD34 for accelerated re-endothelialization after stent implantation [17,18,19,20] Another promising therapeutic strategy is the coating of stents with agents at the molecular level. The short double-stranded 21- to 23-nucleotide-long siRNAs interfere with its complementary messenger RNA (mRNA) which is subsequently degraded [12] This powerful and conserved self-defense mechanism in Eukarya has a threefold biological meaning: (1) it helps prevent infections by viral RNA, (2) it regulates and alters gene expression and (3) it controls a certain type of transposon. PLGA seems to provoke less systemic cytotoxicity, considering PLA and PGA naturally
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