Angioplasty with stents is the most important method for the treatment of coronary artery disease (CAD). However, the drug-eluting stents (DES) which have been widely used nowadays have the increased risks of inflammatory reactions and late stent thrombosis (LST) due to the persistence of polymer coatings. To improve the bio-safety, a novel polymer-free composite drug-eluting coating composed of magnetic mesoporous silica nanoparticles (MMSNs) and carbon nanotubes (CNTs) is constructed using the electrophoretic deposition (EPD) method in this study. A crack-free two-layered coating with impressive "network" nanotopologies is successfully obtained by regulating the composition and structures. This nanostructured coating exhibits excellent mechanical flexibility and blood compatibility in vitro, and the drug-loading and release performance is satisfactory as well. The in vivo study shows that this composite coating has obvious advantages of rapid endothelialization due to its unique 3D nanostructured topologies in comparison with the commercial polymer-coated DES. This study is aimed to provide new ideas and reliable data to design novel functional coatings which could accelerate the re-endothelialization process and avoid inflammatory reactions, thus improving the in vivo bio-safety of DES.