Oxidative stress and vascular inflammation predominantly influence restenosis following angioplasty, causing neointimal hyperplasia. Conventional antioxidants are rapidly eliminated and inadequately localized to injured vessels. We evaluated nitroxide radical-containing nanoparticles (RNPs), polymeric micelles covalently conjugated with 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, in a rat carotid artery balloon injury model. Rhodamine-labeled RNPs selectively accumulated at the injured endothelium and penetrated into the neointima and media. RNPs significantly reduced intimal area, intima-to-media ratio, and preserved lumen patency compared with saline and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL). Mechanistic analyses revealed suppression of reactive oxygen species and oxidized low-density lipoprotein accumulation, LOX-1 expression attenuation, E-selectin–positive endothelial cell reduction, and decreased proinflammatory M1 macrophage infiltration. These findings demonstrate that RNPs effectively suppress angioplasty-induced neointimal hyperplasia through selective vascular accumulation and sustained radical scavenging. Therefore, antioxidant nanomedicine represents a promising therapeutic approach distinct from conventional antioxidants or drug-eluting stents, with translational potential for restenosis prevention.
Watanabe et al. (Thu,) studied this question.