Biodegradable Nanoglobular Magnetic Resonance Imaging Contrast Agent Constructed with Host–Guest Self-Assembly for Tumor-Targeted Imaging

Gadolinium-based macromolecular magnetic resonance imaging (MRI) contrast agents (CAs) have attracted increasing interest in tumor diagnosis. However, their practical application is potentially limited because the long-term retention of gadolinium ion in vivo will induce toxicity. Here, a nanoglobular MRI contrast agent (CA) PAMAM-PG-g-s-s-DOTA(Gd) + FA was designed and synthesized on the basis of the facile host–guest interaction between β-cyclodextrin and adamantane, which initiated the self-assembly of poly(glycerol) (PG) separately conjugated with gadolinium chelates by disulfide bonds and folic acid (FA) molecule onto the surface of poly(amidoamine) (PAMAM) dendrimer, finally realizing the biodegradability and targeting specificity. The nanoglobular CA has a higher longitudinal relaxivity (r1) than commercial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), showing a value of 8.39 mM–1 s–1 at 0.5 T, and presents favorable biocompatibility on the observations of cytotoxicity and tissue toxicity. Furthermore, MRI on cells and tumor-bearing mice both demonstrate the obvious targeting specificity, on the basis of which the effective contrast enhancement at tumor location was obtained. In addition, this CA exhibits the ability of cleavage to form free small-molecule gadolinium chelates and can realize minimal gadolinium retention in main organs and tissues after tumor detection. These results suggest that the biodegradable nanoglobular PAMAM-PG-g-s-s-DOTA(Gd) + FA can be a safe and efficient MRI CA for tumor diagnosis.