Tumor-Inhibitory Effect and Immunomodulatory Activity of Fullerol C 60 (OH) x

Beijing National Laboratory for Molecular Sciences, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P.R. China.
Small (Impact Factor: 7.51). 08/2008; 4(8):1168-75. DOI: 10.1002/smll.200701219
Source: PubMed

ABSTRACT The tumor-inhibitory effect of C60(OH)x was tested on the murine H22 hepatocarcinoma model. Doses of 0.2 and 1.0 mg kg(-1) body weight both showed significant antitumor activity with tumor inhibition rates of 31.9 and 38.4%, respectively, when mice were treated for 17 consecutive days. The damnification of liver was prominently reduced. Furthermore, histological examination indicated that an envelope of fibroblasts and lymphocytes was formed surrounding tumor tissues in the C60(OH)x-treated group, which inhibited the infiltration of tumor to the neighboring normal skeleton muscle tissues. To understand the antitumor mechanism, the immunomodulatory activity of C60(OH)x was investigated. The results indicate that C60(OH)x enhances the phagocytosis of peritoneal macrophages and elevates the activity of arginase and acid phosphatase in vivo. The tumor necrosis factor alpha production of C60(OH)x-treated macrophages also increases in vitro. These results suggest that C60(OH)x can enhance the innate immunity of tumor-bearing mice, and therefore inhibits growth of the tumor.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Strategic design of gadofullerene derivatives is critical to integrate multifunctionality into one entity. Herein, an easy method was developed to fabricate a new type of magnetic resonance imaging/fluorescent integrative molecular imaging probe based on Gd@C-82. The functionalized gadofulleride Gd@C82O similar to 14(OH)(similar to 14)(NH2)(similar to 6) not only exhibits an order of magnitude larger relaxivity (47.0 +/- 0.8 mM(-1) s(-1) at 0.5 T) than commercially used gadopentetic acid (4.5 +/- 0.1 mM(-1) s(-1)) under the same condition and multi-wavelength emission features derived from the multi-wavelength excitation for dual-modality diagnosis, but also highly efficient scavenging capability toward hydroxyl radicals.
    Carbon 12/2013; 65:175-180. DOI:10.1016/j.carbon.2013.08.011 · 6.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Doxorubicin (Dox) is one of the most potent anticancer drugs, but its successful use is hampered by high toxicity caused mainly by generation of reactive oxygen species. One approach to protect against Dox-dependent chemical insult is combined use of the cytostatic drug with antioxidants. C60 fullerene has a nanostructure with both antioxidant and antitumor potential and may be useful in modulating cell responses to Dox. Objective The aim of this study was to estimate the antitumor effect and antioxidant enzyme activity of combined C60 fullerene and Dox (C60 + Dox) in the liver and heart of mice with Lewis lung carcinoma compared with Dox treatment alone. Methods Highly stable pristine C60 fullerene aqueous colloid solution (concentration 1.0 mg/ml, average hydrodynamic diameter of nanoparticles 50 nm) was used in the study and characterized by means of atomic force microscopy (AFM). The in vivo investigation of C60-Dox action was performed via the standard methods of histological and enzyme activity analyses. Results Dox (total dose 2.5 mg/kg) combined with C60 fullerene (total dose 25 mg/kg) in tumor-bearing animals resulted in tumor growth inhibition, prolongation of life, metastasis inhibition, and increased number of apoptotic tumor cells and was more effective than the corresponding course of Dox treatment alone. C60 fullerene demonstrated a protective effect against superoxide dismutase and glutathione peroxidase inhibition induced by Dox-dependent oxidative insult in the liver and heart. Conclusion Combined treatment with C60 + Dox is considered to be a promising approach for cancer chemotherapy.
    Drugs in R & D 12/2014; 14(4). DOI:10.1007/s40268-014-0074-4 · 1.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Development of nanocarriers for effective drug delivery to molecular targets in tumor cells is a real problem in modern pharmaceutical chemistry. In the present work we used pristine C60 fullerene as a platform for delivery of anticancer drug doxorubicin (Dox) to its biological targets. The formation of a complex of C60 fullerene with Dox (C60 + Dox) is described and physico–chemical characteristics of such complex are presented. It was found that Dox conjugation with C60 fullerene leads to 1.5-2-fold increase in Dox toxicity towards various human tumor cell lines, compared with such effect when the drug is used alone. Cytotoxic activity of C60 + Dox complex is accompanied by an increased level of cell produced hydrogen peroxide at early time point (3 h) after its addition to cultured cells. At the same time, cellular production of superoxide radicals does not change in comparison with the effect of Dox alone. Cytomorphological studies have demonstrated that C60 + Dox complexes kill tumor cells by apoptosis induction. The results of in vivo experiments using Lewis lung carcinoma in mice confirmed the enhancement of the Dox toxicity towards tumor cells after drug complexation with C60 fullerene. The effect of such complex towards tumor-bearing mice was even more pronounced than that in the in vitro experiment with targeting human tumor cells. The tumor volume decreased by 2.5 times compared with the control, and an average life span of treated animals increased by 63% compared with control. The obtained results suggest a great perspective of application of C60 + Dox complexes for chemotherapy of malignant tumors.
    Journal of Biomedical Nanotechnology 01/2015; 11(7). DOI:10.1166/jbn.2015.2058 · 7.58 Impact Factor