An intelligent T1-T2 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.

Automated summary

The study proposes a macrophage-targeted and in situ stimuli-triggered T-1-T-2 switchable magnetic resonance imaging (MRI) nanoprobe for non-invasive diagnosis of vulnerable plaques, which can help identify vulnerable plaques at early stages. By modifying and transforming iron oxide nanoparticles, the nanoprobe achieves a substantial non-invasive diagnosis of vulnerable plaques, contributing significantly to the application of materials science in solving clinical problems.