Evaluation of a smart activatable MRI nanoprobe to target matrix metalloproteinases in the early-stages of abdominal aortic aneurysms

Abstract

Matrix metalloproteinases (MMPs) activation contributes to abdominal aortic aneurysm (AAA) growth and rupture. The study was to evaluate the ability of a novel activatable magnetic resonance imaging (MRI) nanoprobe, to target MMPs in an Angiotensin II (ANG II)-induced AAA model. The activatable nanoprobe is composed of a hydrophilic polyethylene glycol coating layer immobilized on the external surface of core/shell Fe/iron oxide nanoparticles; between them, there was grafted the MMP peptide substrate. In the ANG II infusion mice model of AAAs, MRI was performed to characterize the progression of model. The contrast-to-noise ratio was lower in the aneurysm of the mice injected with activatable nanoprobe. Histological studies revealed the presence of MMPs and iron-oxide in regions of MR signal decrease. MRI combined with nanoprobe allows the detection of MMP activity within the wall of AAA, thus representing a potential noninvasive method to predict the rupture risk of AAA.

Keywords: Aneurysm; MMP; MRI; Superparamagnetic iron oxide.