Development of Gd 3 N@C 80 encapsulated redox nanoparticles for high-performance magnetic resonance imaging.

As novel magnetic resonance imaging (MRI) contrast agent, gadofullerene encapsulated redox nanoparticles (Gd3 NPs) were prepared by encapsulation of Gd3 N@C80 in the core of core-shell-type polymer micelles composed of original polyamine with a reactive oxygen species (ROS)-scavenging ability. Because Gd3 NPs possess biocompatible PEG shell with a smaller size (ca. 50 nm), they had high colloidal stability in a physiological environment, and showed low cytotoxicity. Specific accumulation of Gd3 NPs in a tumor was confirmed in tumor-bearing mice after systemic administration. The tumor/muscle (T/M) ratio of the Gd ion reached five at 7.5 h after the administration. T1 -weighted MRI signal enhancement of the T/M ratio increased by 8% at 6 h postinjection of Gd3 NPs (Gd dose:14.35 μmol/kg). Although Gd3 NPs showed a tendency for extended blood circulation, they did not have severe adverse effects, probably due to the confinement of Gd in a hydrophobic fullerene in addition to the ROS-scavenging capacity of these nanoparticles. In sharp contrast, systemic administration of Gd-chelate nanoparticles (GdCNPs) to mice disrupts liver function, increases leukocyte counts, and destroys spleen and skin tissues. Leaking of Gd ions from GdCNPs may cause such adverse effects. Based on these results, we expect that Gd3 NPs is high-performance MRI contrast agents for tumor diagnosis.