Macrophage-targeted and clearable glutathione-based MRI nanoprobes for atherosclerosis molecular imaging

Foam macrophage infiltration is one of the clinical features of high-risk atherosclerotic plaques. Many imaging modalities such as magnetic resonance imaging (MRI) have been used to detect foam macrophages for evaluating plaque vulnerability. However, targeting efficiency, biocompatibility, and clearance remain pivotal challenges in design of new MRI contrast agents. Herein, we report a sensitive, class AI scavenger receptors (SR-AI)-targeted, glutathione-biomineralized gadolinium-based nanoparticle for noninvasive precise MR imaging of macrophages within carotid atherosclerotic lesions in apoE-deficient (ApoE^−/−) mice. The resultant PP1 (16-mer peptide, LSLERFLRCWSDAPAK)-gold-gadolinium nanoparticles (NPs) possessed superior stability, prominent longitudinal relaxivity, and negligible cytotoxicity. In vitro results showed the highest internalization in activated macrophages and in vivo MR images revealed signal augment in carotid atherosclerotic lesions after PP1-gold-gadolinium NP administration at 4 h and 12 h, which were strong testimonial to the formidable macrophage-targeting ability and the subsequent atherosclerosis-retention biofunctions. To summarize, our tactically elaborated biocompatible multifunctional MR NPs integrate T1 signal amplification, precise macrophage targeting, and systematic clearance capabilities, which offer an innovative strategy for noninvasively characterizing vulnerable plaques of early-stage atherosclerosis, or for a wide range of clinical diagnosis and treatment applications.