Cabbage Exosome-Like Nanoparticles Encapsulating Small Noncoding tsRNA Prevent Postinjury Arterial Restenosis

Postinjury restenosis is a common complication of peripheral arterial disease treated via endovascular techniques. Its pathogenesis mainly involves neointimal hyperplasia and persistent inflammation. Although antiproliferative drugs used clinically can temporarily slow restenosis, their effects are limited by short action duration and lack of precise regulation. In this investigation, tRF-49:69-chrM.Trp-TCA (tRF-Trp-TCA) was identified through sequencing data from an animal restenosis model, and its regulatory effects on endothelial cell migration and inflammation were confirmed. Additionally, we discovered that cabbage exosome-like nanoparticles (CELNs) could precisely target injured blood vessels in vivo, enhance the stability of nucleic acid therapeutics, and more effectively inhibit neointimal hyperplasia in a carotid artery balloon injury model. Our results demonstrated that tRF-Trp-TCA is crucial in restenosis induced by arterial injury and CELNs loaded with tRF-Trp-TCA effectively inhibit neointimal hyperplasia following carotid artery injury in rats, showing good biocompatibility. This study has, for the first time, identified the target tRF-Trp-TCA for treating restenosis after vascular injury and has also, for the first time, used CELNs as the delivery system. This discovery could provide new insights for noninvasive treatments or mitigation of restenosis post-endovascular therapy.