title: Development of Gd3N@C80encapsulated redox nanoparticles for high-performance magnetic resonance imaging.
abstract: As novel magnetic resonance imaging (MRI) contrast agent, gadofullerene encapsulated redox nanoparticles (Gd3NPs) were prepared by encapsulation of Gd3N@C80in the core of core-shell-type polymer micelles composed of original polyamine with a reactive oxygen species (ROS)-scavenging ability. Because Gd3NPs 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 Gd3NPs 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 Gd3NPs (Gd dose:14.35 μmol/kg). Although Gd3NPs 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 Gd3NPs is high-performance MRI contrast agents for tumor diagnosis.
authors.affiliation: a Department of Materials Science , Graduate School of Pure and Applied Sciences, University of Tsukuba , Tsukuba , Japan.|b Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences , University of Tsukuba , Tsukuba , Japan.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Gao
authors.affiliation: c Department of Chemistry & Institute for Advanced Research , Nagoya University , Nagoya , Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: c Department of Chemistry & Institute for Advanced Research , Nagoya University , Nagoya , Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Noda
authors.affiliation: c Department of Chemistry & Institute for Advanced Research , Nagoya University , Nagoya , Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Omachi
authors.affiliation: c Department of Chemistry & Institute for Advanced Research , Nagoya University , Nagoya , Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Shinohara
authors.affiliation: d Department of Analytical and Bioinorganic Chemistry , Kyoto Pharmaceutical University , Kyoto , Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: a Department of Materials Science , Graduate School of Pure and Applied Sciences, University of Tsukuba , Tsukuba , Japan.|b Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences , University of Tsukuba , Tsukuba , Japan.|e Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS) , University of Tsukuba , Tsukuba , Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
mesh_terms: D000818:Animals; D002214:Capsules; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D037741:Fullerenes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D005682:Gadolinium / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010084:Oxidation-Reduction
chemical_list: D002214:Capsules; D003287:Contrast Media; D037741:Fullerenes; D005682:Gadolinium
keywords: Gd3N@C80 encapsulated redox nanoparticles; Magnetic resonance imaging; drug delivery system; fullerene; reactive oxygen species