The (PrS/HGF‐pDNA) multilayer films for gene‐eluting stent coating: Gene‐protecting, anticoagulation, antibacterial properties, and in vivo antirestenosis evaluation

Abstract

Vascular gene-eluting stents (GES) is a promising strategy for treatment of cardiovascular disease. Very recently, we have proved that the (protamine sulfate/plasmid DNA encoding hepatocyte growth factor) (PrS/HGF-pDNA) multilayer can serve as a powerful tool for enhancing competitiveness of endothelial cell over smooth muscle cell, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. However, before the gene multilayer films could be used in vascular stents for real clinical application, the preservation of gene bioactivity during the industrial sterilization and the hemocompatibility of film should be taken into account. Actually, both are long been ignored issues in the field of gene coating for GES. In this study, we demonstrate that the (PrS/HGF-pDNA) multilayer film exhibits the good gene-protecting abilities, which is confirmed by using the industrial sterilizations (gamma irradiation and ethylene oxide) and a routine storage condition (dry state at 4°C for 30 days). Furthermore, hemocompatible measurements (such as platelet adhesion and whole blood coagulation) and antibacterial assays (bacteria adhesion and growth inhibition) indicate the good anticoagulation and antibacterial properties of the (PrS/HGF-pDNA) multilayer film. The in vivo preliminary data of angiography and histological analysis suggest that the (PrS/HGF-pDNA) multilayer coated stent can reduce the in-stent restenosis. This work reveals that the (PrS/HGF-pDNA) multilayer film could be a promising candidate as coating for GES, which is of great potential in future clinic application.

Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis

“…Thick polymeric coatings initially used for bulk immobilization of the vector depot were shown to be highly pro-inflammatory 29 and thus unsuitable in the context of therapeutic GDS. This problem motivated us 7 – 9 , 30 and others 31 , 32 to develop techniques for stent immobilization of gene vectors that rely on reversible tethering of vector particles directly to modified metal surfaces of stents thus avoiding the inflammatory reactions triggered by polymeric coatings. Unlike our prior work that used direct attachment of vector-binding moieties to polyallylamine bisphosphonate-modified steel 8 , our present studies employed a universal adaptor, PrG that exhibits a strong affinity to the Fc fragments of mammalian IgG 33 and can thus be used as a molecular bridge between the stent surface and vector binding antibody.…”

Advances in stent-mediated gene delivery

“…An important consideration has been effective and safe delivery of gene to target lesion using vectors. Various approaches are employed, including coated and coatless techniques [3,4]; naked plasmids have shown ineffective gene transduction and efforts have been directed to increase plasmid stability to improve efficiency by adding liposomes and polymers. Although these strategies protect plasmids from early digestion and allow their increase of cellular uptake, these approaches lose cellular targeting.…”

Achievements and Prospects in the Field of Gene-Eluting Coronary Stents

“…Достижения и перспективы в области разработки ген-выделяющих коронарных стентов кодирующей фактор роста гепатоцитов, продемон-стрировало успешную доставку генетического ма-териала в преклинической модели [8]. Аденовирусные (Ad) векторы являются двух-цепочечными ДНК-векторами, которые входят в клетку путем эндоцитоза с помощью коксаки-аде-новирусного рецептора.…”