Inhibition of Tumor Growth by Endohedral Metallofullerenol Nanoparticles Optimized as Reactive Oxygen Species Scavenger

• Published in: Molecular pharmacology 2008-10, Vol.74 (4), p.1132-1140
• Main Authors: Yin, Jun-Jie, Lao, Fang, Meng, Jie, Fu, Peter P, Zhao, Yuliang, Xing, Gengmei, Gao, Xueyun, Sun, Baoyun, Wang, Paul C, Chen, Chunying, Liang, Xing-Jie
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Animals; Cell Line, Tumor; Female; Fullerenes - chemistry; Fullerenes - therapeutic use; Gadolinium - therapeutic use; Humans; Lipid Peroxidation - drug effects; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Membrane Potential, Mitochondrial - drug effects; Mice; Mice, Nude; Mitochondria - enzymology; Mitochondria - metabolism; Nanostructures - chemistry; Nanostructures - therapeutic use; Nanotechnology - methods; Neoplasms - drug therapy; Neoplasms - pathology; Organometallic Compounds - chemistry; Organometallic Compounds - therapeutic use; Oxidative Stress - drug effects; Oxidoreductases - metabolism; Reactive Oxygen Species - analysis; Reactive Oxygen Species - metabolism; Time Factors; Tumor Burden - drug effects; Xenograft Model Antitumor Assays - methods
• ISSN: 0026-895X; 1521-0111
• DOI: 10.1124/mol.108.048348

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. Like-wise, 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.