RNA Eluting Surfaces for the Modulation of Gene Expression as a Novel Stent Concept

Objectives: A new era of drug eluting stents (DESs) is in progress to improve late adverse effects like neointimal hyperplasia after coronary stent implantation in atherosclerotic vessels. Gene expression modulating stents might have the potential as a new promising therapeutic strategy releasing specific small interfering RNAs (siRNAs) or messenger RNAs (mRNAs) to the vascular wall for better regeneration and inhibition of adverse effects.

Methods: Three different poly (lactic-co-glycolic acid) (PLGA) resomers were tested for their ability as a gene delivery carrier of siRNA against intercellular adhesion molecule (ICAM)-1 with depot effect.

Results: Biodegradability, hemocompatibility, and high cell viability was found in all PLGAs. We achieved PLGA coatings with incorporated siRNA, which were able to transfect EA.hy926 and human vascular endothelial cells (hVECs), leading to siRNA mediated knockdown. Furthermore, we achieved co-transfection of siRNA and mRNA leading to the expression of enhanced green fluorescent protein (eGFP), next to siRNA transfection. With our multilayer build-up of PLGA and siRNA layers we reached high transfection efficiency until day six and long-lasting transfection until day 20.

Conclusion: Our results indicate that siRNA and mRNA nanoparticles incorporated in PLGA films have the potential for modulating gene expression after stent implantation to achieve accelerated regeneration and reduce the risk of restenosis.

No conflict of interest has been declared by the author(s).