TY - JOUR T1 - Inhibition of Tumor Growth by Endohedral Metallofullerenol Nanoparticles Optimized as Reactive Oxygen Species Scavenger JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1132 LP - 1140 DO - 10.1124/mol.108.048348 VL - 74 IS - 4 AU - Jun-Jie Yin AU - Fang Lao AU - Jie Meng AU - Peter P. Fu AU - Yuliang Zhao AU - Gengmei Xing AU - Xueyun Gao AU - Baoyun Sun AU - Paul C. Wang AU - Chunying Chen AU - Xing-Jie Liang Y1 - 2008/10/01 UR - http://molpharm.aspetjournals.org/content/74/4/1132.abstract N2 - Intraperitoneal injection of [Gd@C82(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@C82(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. Like-wise, studies using ESR with spin-trapping demonstrated efficient scavenging of superoxide radical anion, hydroxyl radical, and singlet oxygen (1O2) by [Gd@C82(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@C82(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@C82(OH)22]n nanoparticles reduced H2O2-induced ROS formation and mitochondrial damage. [Gd@C82(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@C82(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@C82(OH)22]n nanoparticles on tumor growth likely relates with typical capacity of scavenging reactive oxygen species. The American Society for Pharmacology and Experimental Therapeutics ER -