Rapamycin-loaded nanocoating to specially modulate smooth muscle cells on ZE21B alloy for vascular stent application

Abstract

Drug-eluting stents (DES) are widely used in the treatment of cardiovascular diseases. However, the therapeutic drugs eluted from the drug-loaded coatings on DES usually have no selectivity for vascular cells and cause delayed endothelialization. In this work, a rapamycin-loaded nanocoating consisting of the MgF2 layer, polydopamine layer, and targeted rapamycin-loaded nanoparticles (NPs) was constructed on Mg-Zn-Y-Nd (ZE21B) alloy to improve its corrosion resistance and specially modulate smooth muscle cells (SMCs) for vascular stent application. The rapamycin-loaded NPs released from the nanocoating on ZE21B alloy can selectively target vascular SMCs via the receptor-ligand interaction on SMCs, thereby improving drug availability and reducing side effects. The results of electrochemical corrosion tests confirmed the enhanced corrosion resistance of modified ZE21B alloy. The well hemocompatibility of modified ZE21B alloy was verified by the hemolysis tests, platelet adhesion assays, and fibrinogen adhesion/activation assays. The results of in vitro cell experiments indicated that the rapamycin-loaded nanocoating on ZE21B alloy selectively inhibited the proliferation and migration of vascular SMCs, and while had the relatively weak effects on the proliferation of vascular endothelial cells (ECs). These promising results suggested the potential of SMCs-targeting rapamycin-loaded nanocoating to improve corrosion resistance and prevent in-stent restenosis of biodegradable cardiovascular implants.