Continuous NO dual-generation by ZnO nanoparticle conjugated with α-lipoic acid for functional biodegradable vascular stent

Abstract

Coronary artery diseases are treated with a biodegradable vascular scaffold (BVS) intervention. However, BVS need to be enhanced to avoid post-insertion side effects, which can be done by controlling the nitric oxide (NO) concentration in blood vessels. NO has excellent functions, such as re-endothelialization, inhibition of smooth muscle cells, and prevention of activation and aggregation of platelets, and is essential in maintaining a healthy heart and blood vessels. In this study, a novel nanoparticle with fortified NO-generating ability was synthesized by combining two mechanisms capable of long-term NO production: the decomposition of the NO donor by the redox reaction of zinc oxide and the thiol/disulfide exchange reaction between the NO donor and α-lipoic acid. Next, a poly(L-lactic acid) (PLLA) scaffold containing synthesized nanoparticles was fabricated, and the potent functional recovery ability of unhealthy vessels was demonstrated in vitro and in vivo. The NO generated from scaffolds inhibited platelet adhesion and activation, increased endothelial cell proliferation, and decreased smooth muscle cell proliferation. In addition, the scavenging ability of reactive oxygen species and their inhibition of toxic NO production were investigated. The scaffolds implanted subcutaneously in mice suppressed the inflammatory response and induced healthy blood vessel formation, offering a new tool for designing cardiovascular stents and various biological applications.