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: 8.37). 08/2008; 4(8):1168-75. DOI: 10.1002/smll.200701219
Source: PubMed


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.

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    • "In contrast to our data, Liu et al17 reported an activation of TH1 cells and a strong increase in TNF-α as well as IL-6 production in vivo and in vitro in tumor-bearing and healthy mice using C60(OH)20 nanoparticles, and similar effects were also observed by Zhu et al.20 Furthermore, a C82 fullerene entrapped with a gadolinium derivative atom in the core of the carbon cage19, used as a new generation of MRI contrast agent46 has rather proinflammatory properties. Thus, in their animal model the authors found a TH1-polarizing effect, which was also obtained when they used human dendritic cells. "
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    ABSTRACT: C60 nanoparticles, the so-called buckminsterfullerenes, have attracted great attention for medical applications as carriers, enzyme inhibitors or radical scavengers. However, publications evaluating their immunological mechanisms are still rather limited. Therefore, we aimed to analyze systematically the in vitro influence of polyhydroxy-C60 (poly-C60) and N-ethyl-polyamino-C60 (nepo-C60) on peripheral blood mononuclear cells (PBMC) from healthy individuals, angling their effect on proliferation, expression of surface markers, and cytokine production. We isolated PBMC from 20 healthy subjects and incubated them in a first step only with poly-C60 or nepo-C60, and in a second step together with recall antigens (purified protein derivative, tetanus toxoid, bacillus Calmette-Guérin). Proliferation was determined by (3)H-thymidine incorporation, activation of PBMC-subpopulations by flow cytometry by measurement of the activation marker CD69, and secretion of T helper cell type 1 (TH1)- (interferon-gamma [IFN-γ], tumor necrosis factor beta [TNF-β]), TH2- (interleukin-5 [IL-5], -13, -10) and macrophage/monocyte-related cytokines (IL-1, IL-6, TNF-α) into the supernatants by enzyme-linked immunosorbent assay. Both fullerenes did not influence T cell reactivity, with no enhanced expression of CD69 and production of T cell cytokines observed, the CD4/CD8 ratio remaining unaffected. In contrast, they significantly enhanced the release of IL-6 and CD69-expression by CD56 positive natural killer cells. PBMC, which had been cultured together with the three recall antigens were not affected by both fullerenes at all. These data indicate that fullerenes do not interact with T cell reactivity but may activate cells of the innate immune system. Furthermore, they seem to act only on 'naïve' cells, which have not been prestimulated with recall antigens, there are however, large inter individual differences.
    Full-text · Article · Aug 2012 · International Journal of Nanomedicine
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    • "Since 1993 countless studies showed that [60]fullerene (C 60 ) and derivatives exhibit paramount potentialities in several fields of biology and medicine [1] mainly including specific DNA cleavage, imaging [2], UV and radioprotection [3], antiviral, antioxidant, and anti-amyloid activities [1,4e7], allergic response [8] and angiogenesis [9] inhibitions, immune stimulating and antitumour effects [10] [11], enhancing effect on neurite outgrowth [12], gene delivery [13], and even hair-growing activity [14]. However, although several independent research groups confirmed the innocuousness of pristine C 60 [15e17] the toxicity of this fullerene is still a matter of debate [18] [19]. "
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    ABSTRACT: Countless studies showed that [60]fullerene (C(60)) and derivatives could have many potential biomedical applications. However, while several independent research groups showed that C(60) has no acute or sub-acute toxicity in various experimental models, more than 25 years after its discovery the in vivo fate and the chronic effects of this fullerene remain unknown. If the potential of C(60) and derivatives in the biomedical field have to be fulfilled these issues must be addressed. Here we show that oral administration of C(60) dissolved in olive oil (0.8 mg/ml) at reiterated doses (1.7 mg/kg of body weight) to rats not only does not entail chronic toxicity but it almost doubles their lifespan. The effects of C(60)-olive oil solutions in an experimental model of CCl(4) intoxication in rat strongly suggest that the effect on lifespan is mainly due to the attenuation of age-associated increases in oxidative stress. Pharmacokinetic studies show that dissolved C(60) is absorbed by the gastro-intestinal tract and eliminated in a few tens of hours. These results of importance in the fields of medicine and toxicology should open the way for the many possible -and waited for- biomedical applications of C(60) including cancer therapy, neurodegenerative disorders, and ageing.
    Full-text · Article · Apr 2012 · Biomaterials
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    • "In 2005, we found that gadolinium endohedral metallofullerenol (Gd@C82(OH)n nanoparticles) can efficiently inhibit the growth of murine H22 hepatoma without obviously adverse effects on important organs, having nearly no direct toxic effect to tumor cells 40, which is an advantage over conventional anti-tumor drugs. Zhu et al. 41 also tested the tumor-inhibitory effect of C60(OH)x on the same model. In the C60(OH)x-treated group, significant tumor inhibition rates and reduced damage to liver were shown, in accordance to the histological results of inhibited tumor infiltration. "
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    ABSTRACT: Functionalized fullerenes with specific physicochemical properties have been developed for cancer diagnosis and therapy. Notably, metallofullerene is a new class of magnetic resonance imaging (MRI) contrast-enhancing agent, and may have promising applications for clinical diagnosis. Polyhydroxylated and carboxyl fullerenes have been applied to photoacoustic imaging. Moreover, in recent years, functionalized fullerenes have shown potential in tumor therapies, such as photodynamic therapy, photothermal treatment, radiotherapy and chemotherapeutics. Their antitumor effects may be associated with the modulation of oxidative stress, anti-angiogenesis, and immunostimulatory activity. While various types of novel nanoparticle agents have been exploited in tumor theranostics, their distribution, metabolism and toxicity in organisms have also been a source of concern among researchers. The present review summarizes the potential of fullerenes as tumor theranostics agents and their possible underlying mechanisms are discussed.
    Full-text · Article · Mar 2012 · Theranostics
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