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

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 T 1 - T 2 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 T 1 MRI enhancement ( r 2 / r 1 = 3.415). Triggered by the low pH environment of macrophage lysosomes, the single-dispersed IONP-HP transforms into a cluster analogue, which exhibits T 2 MRI enhancement ( r 2 / r 1 = 13.326). Furthermore, an in vivo switch of T 1 - T 2 enhancement modes shows that the vulnerable plaques exhibit strong T 1 enhancement after intravenous administration of the nanoprobe, followed by a switch to T 2 enhancement after 9 h. In contrast, stable plaques show only slight T 1 enhancement but without T 2 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 T 1 - T 2 switchable process, which will significantly contribute to the application of materials science in solving clinical problems. A T 1 - T 2 switchable MRI contrast agent, hyaluronic acid-modified iron oxide nanoparticle-polyacrylic acid, is used for the identification of vulnerable atherosclerotic plaques by macrophage phagocytosis. It could reveal promising enhancement in MRI.