Reduction-Responsive Nucleic Acid Delivery Systems To Prevent In-Stent Restenosis in Rabbits

Abstract

Cardiovascular and cerebrovascular ischemic diseases seriously affect human health. Endovascular stent placement is an effective treatment but always leads to in-stent restenosis (ISR). Gene-eluting stent, which combines gene therapy with stent implantation, is a potential method to prevent ISR. In this study, an efficient gene-eluting stent was designed on the basis of one new nucleic acid delivery system to decrease the possibility of ISR. The reduction-responsive branched nucleic acid vector (SKP) with low cytotoxicity was first synthesized via ring-opening reaction. The impressive in vitro transfection performances of SKP were proved using luciferase reporter, enhanced green fluorescent protein plasmid, and vascular endothelial growth factor plasmid (pVEGF). Subsequently, SKP/pVEGF complexes were coated on the surfaces of pretreated clinical stents to construct gene-eluting stents (S-SKP/pVEGF). Antirestenosis performance of S-SKP/pVEGF was evaluated via implanting stents into rabbit aortas. S-SKP/pVEGF could lead to the localized upregulation of VEGF proteins, improve the progress of re-endothelialization, and inhibit the development of ISR in vivo. Such efficient pVEGF-eluting stent with responsive nucleic acid delivery systems is very promising to prevent in-stent restenosis of cerebrovascular diseases.

Endothelial Cell-Mediated Gene Delivery for In Situ Accelerated Endothelialization of a Vascular Graft

“…Besides, all modified surfaces were relatively rough. The PDA coating was a type of simple and effective method of introducing functional groups onto the biomaterial surface to facilitate subsequent surface modification . Moreover, the wettability of nanofiber surfaces was determined by the WCA.…”

“…The PDA coating was a type of simple and effective method of introducing functional groups onto the biomaterial surface to facilitate subsequent surface modification. 32 Moreover, the wettability of nanofiber surfaces was determined by the WCA. As shown in Figure 3, the WCA of the PLCL surface was 119.8 ± 1.2°, which reflected its hydrophobic property.…”

Designing Cardiovascular Implants Taking in View the Endothelial Basement Membrane

“…This induced an increased proliferation of EC but not of SMC in vitro, which suggests that HGF is a potential promotor of endothelialization, which also prevents intimal hyperplasia [ 83 ]. Moreover, stents coated with VEGF-expressing plasmids resulted in increased local VEGF concentrations in rabbit aortas, most likely due to transfection of EC as shown in vitro, and improved endothelialization, whereas stent stenosis was inhibited [ 84 ]. In this context, aptamers, which are short single-strand nucleic acids fragments or aptamer–peptide complexes, were also studied regarding their potential to recruit EC.…”

Surface Engineering of Cardiovascular Devices for Improved Hemocompatibility and Rapid Endothelialization

“…Biological experiments indicated that S-SKP/pVEGF stents locally upregulated VEGF expression, promoted re-endothelialization and prevented in-stent restenosis. [301] From these above and other similar studies, [302] the surface-mediated gene delivery systems possess great potential in the field of cardiovascular implants.…”