A Protein Corona-Based Diagnostic Tool for Eroded Atherosclerotic Plaques

Superficial plaque erosion, distinct from plaque rupture, represents a cause of residual thrombotic complications in atherosclerosis. Being able to detect plaque erosion, a mechanism that now accounts for up to 30% of acute coronary syndromes, can lead to targeted therapies, and perhaps avoid the need for urgent invasive interventions required for plaque rupture cases, thus greatly affecting clinical management. Nanoparticles (NPs) exposed to biological fluids acquire a layer of proteins on their surface, the protein corona (PC). Variations in the composition of the plasma proteome occurring in pathological conditions directly influence the composition of the PC. An NP-based diagnostic approach is presented exploiting the proteomic changes at the nano-bio interface for superficial plaque erosion detection. To this aim, an in vivo experimental murine procedure is used that recapitulates features of the pathophysiological conditions of superficial erosion. Two types of metal-organicframework (MOF) NPs for PC generation are employed: zirconium and iron (III) MOF (ZrMOF and FeMOF). It is demonstrated that Zr-MOF NPs act as plasma protein concentrators allowing the identification of a higher number of proteins, compared to unfractionated analysis of plasma. Nonetheless, It is identified thirteen plasma proteins exclusive to the superficial erosion group that might serve as signature proteins to discriminate the pathological condition.