Journal
MOLECULAR PHARMACOLOGY
Volume 74, Issue 4, Pages 1132-1140Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/mol.108.048348
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Funding
- Chinese Academy of Sciences (CAS) [07165111ZX]
- 973 Programs [2006CB705600]
- Natural Science Foundation of China [10525524, 20751001]
- National Institutes of Health/National Center for Research Resources/Research Centers in Minority Institutions [2G12RR003048]
- National Institutes of Health [5U 54CA091431]
- U. S. Army Medical Research and Materiel Command [W81XWH-05-1-0291]
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Intraperitoneal injection of [Gd@C(82)(OH)(22)](n) nanoparticles decreased activities of enzymes associated with the metabolism of reactive oxygen species (ROS) in the tumor-bearing mice. Several physiologically relevant ROS were directly scavenged by nanoparticles, and lipid peroxidation was inhibited in this study. [Gd@C(82)(OH)(22)](n) nanoparticles significantly reduced the electron spin resonance (ESR) signal of the stable 2,2-diphenyl-1-picryhydrazyl radical measured by ESR spectroscopy. Likewise, studies using ESR with spin-trapping demonstrated efficient scavenging of superoxide radical anion, hydroxyl radical, and singlet oxygen ((1)O(2)) by [Gd@C(82)(OH)(22)](n) nanoparticles. In vitro studies using liposomes prepared from bovine liver phosphatidylcholine revealed that nanoparticles also had a strong inhibitory effect on lipid peroxidation. Consistent with their ability to scavenge ROS and inhibit lipid peroxidation, we determined that [Gd@C(82)(OH)(22)](n) nanoparticles also protected cells subjected in vitro to oxidative stress. Studies using human lung adenocarcinoma cells or rat brain capillary endothelial cells demonstrated that [Gd@C(82)(OH)(22)](n) nanoparticles reduced H(2)O(2)-induced ROS formation and mitochondrial damage. [Gd@C(82)(OH)(22)](n) nanoparticles efficiently inhibited the growth of malignant tumors in vivo. In summary, the results obtained in this study reveal antitumor activities of [Gd@C(82)(OH)(22)](n) nanoparticles in vitro and in vivo. Because ROS are known to be implicated in the etiology of a wide range of human diseases, including cancer, the present findings demonstrate that the potent inhibition of [Gd@C(82)(OH)(22)](n) nanoparticles on tumor growth likely relates with typical capacity of scavenging reactive oxygen species.
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