Inhibition of tumor growth by endohedral metallofullerenol nanoparticles optimized as reactive oxygen species scavenger.
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.
Yin
Jun-Jie
JJ
Division of Nanomedicine and Nanobiology, National Center for Nanoscience and Technology of China, 11, First North Rd., Zhongguancun, Beijing, People's Republic of China, 100190.
Lao
Fang
F
Meng
Jie
J
Fu
Peter P
PP
Zhao
Yuliang
Y
Xing
Gengmei
G
Gao
Xueyun
X
Sun
Baoyun
B
Wang
Paul C
PC
Chen
Chunying
C
Liang
Xing-Jie
XJ
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D037741:Fullerenes / Q000737:chemistry / Q000627:therapeutic use*; D005682:Gadolinium / Q000627:therapeutic use*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use*; D036103:Nanotechnology / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D037741:Fullerenes; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D005682:Gadolinium; D010088:Oxidoreductases