An intelligent T 1 -T 2 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.