Scavenger receptor-AI-targeted ultrasmall gold nanoclusters facilitate in vivo MR and ex vivo fluorescence dual-modality visualization of vulnerable atherosclerotic plaques

Abstract Owing to the high morbidity and mortality of cardiovascular diseases resulting from atherosclerosis, developing specific noninvasive diagnostic methods to distinguish vulnerable atherosclerotic plaques becomes urgent and mandatory. Herein, scavenger receptors AI (SR-AI), a secreted biomarker associated with foam macrophages, was selected as a target for identifying vulnerable plaques. A dual-modality imaging probe (PP1-Au@GSH@Gd NCs) was constructed by covalently attaching a peptidic SR-AI ligand, PP1 to gadolinium-integrated gold nanoclusters, which exhibited remarkably improved fluorescence signal and longitudinal relaxivity with highly loaded Au and Gd species. In vitro cellular binding studies showed preferential affinity of PP1-Au@GSH@Gd NCs to activated macrophages in SR-AI-dependent manner. In vivo MR/fluorescence images presented robust and prolonged plaque contrast enhancement in established ApoE −/− mice models thanks to favorable targeting efficacy of PP1-Au@GSH@Gd NCs. Collectively, the noninvasive MR/fluorescence molecular imaging strategy with PP1-Au@GSH@Gd NCs holds great promise for precise clinical diagnosis of vulnerable plaques.