An intelligent T1–T2 switchable MRI contrast agent for the non-invasive identification of vulnerable atherosclerotic plaques

Abstract

Unlike stable atherosclerotic plaques, vulnerable plaques are very likely to cause serious cardio-cerebrovascular diseases. Meanwhile, how to non-invasively identify vulnerable plaques at early stages has been an urgent but challenging problem in clinical practices. Here, we propose a macrophage-targeted and in situ stimuli-triggered T₁–T₂ switchable magnetic resonance imaging (MRI) nanoprobe for the non-invasive diagnosis of vulnerable plaques. Precisely, single-dispersed iron oxide nanoparticles (IONPs) modified with hyaluronic acid (HA), denoted as IONP-HP, show macrophage targetability and T₁ MRI enhancement (r₂/r₁ = 3.415). Triggered by the low pH environment of macrophage lysosomes, the single-dispersed IONP-HP transforms into a cluster analogue, which exhibits T₂ MRI enhancement (r₂/r₁ = 13.326). Furthermore, an in vivo switch of T₁–T₂ enhancement modes shows that the vulnerable plaques exhibit strong T₁ enhancement after intravenous administration of the nanoprobe, followed by a switch to T₂ enhancement after 9 h. In contrast, stable plaques show only slight T₁ enhancement but without T₂ enhancement. It is therefore imperative that the intelligent and novel nanoplatform proposed in this study achieves a substantial non-invasive diagnosis of vulnerable plaques by means of a facile but effective T₁–T₂ switchable process, which will significantly contribute to the application of materials science in solving clinical problems.