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RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept
Olivia Koenig1, Diane Zengerle2, Nadja Perle3
1Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany. olivia.koenig@gmx.de.
Pharmaceuticals (Basel, Switzerland)
|February 18, 2017
Summary
Gene-eluting stents using poly (lactic-co-glycolic acid) (PLGA) nanoparticles show potential for improved vessel healing. These stents deliver small interfering RNA (siRNA) and messenger RNA (mRNA) to reduce restenosis after coronary procedures.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cardiovascular Research
Background:
- Drug-eluting stents aim to mitigate late adverse effects like thrombosis post-coronary implantation.
- Gene expression modulation via stents offers a novel strategy for vascular regeneration and inhibiting adverse outcomes.
- Poly (lactic-co-glycolic acid) (PLGA) is explored as a carrier for small interfering RNAs (siRNAs) targeting intercellular adhesion molecule (ICAM)-1.
Purpose of the Study:
- To evaluate PLGA-based nanoparticles as carriers for siRNA and mRNA delivery to vascular cells.
- To assess the efficacy of siRNA-loaded PLGA coatings in transfecting endothelial cells and achieving gene knockdown.
- To determine the potential of these gene-eluting stents in promoting endothelial regeneration and reducing restenosis.
Main Methods:
- Synthesis and characterization of PLGA nanoparticles for siRNA and mRNA incorporation.
- In vitro transfection studies using EA.hy926 and human vascular endothelial cells.
- Assessment of gene knockdown (siICAM-1) and gene expression (eGFP mRNA) post-transfection.
- Evaluation of transfection efficiency and duration using PLGA and siRNA multilayers.
Main Results:
- PLGA nanoparticles demonstrated biodegradability, hemocompatibility, and high cell viability.
- Successful transfection of endothelial cells and significant siICAM-1 knockdown were achieved.
- Co-transfection with siRNA and enhanced green fluorescent protein (eGFP) mRNA resulted in eGFP expression.
- High and long-lasting transfection efficiencies were observed in EA.hy926 cells up to 20 days.
Conclusions:
- PLGA films incorporating siRNA and mRNA nanoparticles are effective for gene expression modulation.
- These gene-eluting stent technologies hold promise for accelerating endothelial regeneration.
- The approach may significantly reduce the risk of restenosis following coronary stent implantation.
