Nanotheranostics of Pre-Stenotic Vessels By Target Touch-On Signaling of Peptide Navigator

Abstract

Navigation of nanoparticles to target sites of blood flow disturbance markedly upgrades the diagnostic paradigm in vascular medicine. The theranostic treatment of pre-stenotic vessels can prevent the irreversible occlusion process effectively. Here, these nanotheranostic functions are established by displaying CDK9(cyclin-dependent kinase 9)-targeting peptide (P.) onto nanovesicles (NV) and liposomes using the navigation function and subsequent binding-on signaling of P. as a game-changer. When rabbit vessels are allografted with injecting contrast-loaded P. liposomes, the case-dependent stenotic degree after 2-6 weeks can be diagnosed accurately within 2-4 days via computed tomography imaging with cross-validation in a mouse model of partial carotid ligation. Furthermore, the anti-CDK9 signaling of P. NV is activated post-targeting and effectively prevents vascular stenosis by suppressing inflammation and lipotoxicity in the vessels, serum, and/or liver. CDK9 targeting is confirmed using computer, in vitro, and in vivo models. This study demonstrates an unprecedented nanotheranostic function for future clinical applications.