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The prolongation of the lifespan of rats by repeated oral administration of [60]fullerene

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... One of the more striking results in C 60 literature was the observation that a small cohort of rats that were dosed with C 60 dissolved in olive oil (C 60 -OO) from youth had extended mean lifespans (90% increase) relative to rats who were only dosed with olive oil (OO) or with nothing at all [14]. This is the largest life-extension effect on rats from a chemical compound seen to date, and it is the only study of C 60 on lifespan. ...
... Due to the potential medical benefits of a small molecule capable of extending lifespan and the discrepancy in reported results, the independent confirmation of the effects of C 60 on lifespan is extremely valuable. Indeed, the previous lifespan results are so compelling that some communities have begun to treat themselves and their domestic pets with C 60 -OO obtained from online vendors, even though the drug product and formulation have not been assessed for toxicity by any regulatory agency [14]. The lack of formulation and storage quality control in these products due to their unregulated nature raises concerns relevant to the public health. ...
... The groups received 1.7-mg/kg dosages of C60-OO or an equivalent volume of unmodified olive oil (OO) via intraperitoneal injection. Mice were injected under a dosage schedule similar to that of previous performed studies by Baati et al [14]. Briefly, the mice received injections daily for the first week, then weekly for 7 weeks, then fortnightly for twenty more weeks. ...
Article
C60 is a potent antioxidant that has been reported to substantially extend the lifespan of rodents when formulated in olive oil (C60-OO) or extra virgin olive oil (C60-EVOO). Despite there being no regulated form of C60-OO, people have begun obtaining it from online sources and dosing it to themselves or their pets, presumably with the assumption of safety and efficacy. In this study, we obtain C60-OO from a sample of online vendors, and find marked discrepancies in appearance, impurity profile, concentration, and activity relative to pristine C60-OO formulated in-house. We additionally find that pristine C60-OO causes no acute toxicity in a rodent model but does form toxic species that can cause significant morbidity and mortality in mice in under 2 weeks when exposed to light levels consistent with ambient light. Intraperitoneal injections of C60-OO did not affect the lifespan of CB6F1 female mice. Finally, we conduct a lifespan and health span study in males and females C57BL/6 J mice comparing oral treatment with pristine C60-EVOO and EVOO alone versus untreated controls. We failed to observe significant lifespan and health span benefits of C60-EVOO or EVOO supplementation compared to untreated controls, both starting the treatment in adult or old age. Our results call into question the biological benefit of C60-OO in aging.
... Since its discovery, fullerene has been actively investigated in the physical, chemical, and biomedical sciences [1][2][3][4][5][6]. The research has provided valuable insights into the molecule and its potential applications in various fields, especially biomedical sciences. ...
... Although several studies have supported its potential role in various applications, fullerene's toxicity profile remains undetermined. Thus, it is essential to explore the molecule's toxicity profile via short-term and long-term toxicity studies in experimental models [2,[5][6][7]. ...
... Fullerene occurs in natural sources. The molecule can be synthesized in the laboratory, vaporizing graphite in an inert gaseous atmosphere [1][2][3][4]. Of the various fullerene shapes, C 60 is spherical with 60 carbon atoms, measuring less than a nanometer. ...
Article
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Fullerene derivatives-most most notably Carbon 60 (C 60)-have been investigated for their beneficial applications in humans. Fullerene, as a super antioxidant, protects cells from the harmful effects of free radicals. They may assist in weight loss, strengthen the immune system, improve the signs of aging, increase longevity, augment sports performance, enhance vitality, and improve quality of life-when used with a balanced diet and exercise. Many C 60 products can be purchased from e-commerce sites for oral consumption. However, the appropriate dose is not provided, or the given doses are not matching among the products. Despite the positive claims regarding their use and anecdotal evidence, none of the C 60 preparations have been approved by the USFDA, MHRA UK, or EMA for human use. Although specific fullerene materials display biocompatibility, there are no short-term or long-term toxicity studies to date. Thus, "buyer beware". Those who choose to ingest such fullerene materials should consider themselves as self-experimenters and the fullerenes not as a bonafide treatment or preventive agent, pending the outcome of future research.
... For the oral C 60 administration in rats, olive oil has usually been used (Baati et al., 2012). However, in animals, the supplementation with vegetable oils could cause liver steatosis (Đurašević et al., 2020), consequently leading to the increase in the level of circulating exosomes, chemokines, cytokines and activated lymphocytes (Guay and https://doi.org/10.1016/j.fct.2020.111302 ...
... The rats of the oil + C 60 (O + F) group (average body mass 432.83 ± 10.98 g) were fed for twelve weeks in the same way as the O-group rats, with the exception that C 60 (Bucky USA, CAS# 99685-96-8, 99%) was previously dissolved in oil in the concentration of 1 mg/ml. This concentration of C 60 in food was selected in order to reach daily fullerene intake of about 5 mg/kg b.m., the dose usually referred to in the literature as high, as opposed to a daily dose of 1 mg/kg being referred to as low (Baati et al., 2012). Due to high insolubility, oil + fullerene solution was stirred at room temperature for one week, covered with aluminium foil to avoid UV irradiation (Cataldo, 2010). ...
... A part of our results is consistent with the previous findings that eight days long oral C 60 supplementation leads to its bioaccumulation of 2.92 ± 0.82 μg/g in the liver, 0.20 ± 0.08 μg/g in the brain, and 51 ± 14 μg/g in the spleen (Baati et al., 2012). The higher liver and lower spleen C 60 bioaccumulation in our experiment is probably the result of the use of olive/coconut oil mixture as the C 60 solvent, in contrast to olive oil use in the experiment of Baati et al. (2012). ...
Article
The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action. Share Link https://authors.elsevier.com/a/1aqjz-NVj4SjF
... 9 C 60 fullerenes show substantial ROS scavenging activity in the model of ROSdependent liver damage (tetrachloride intoxication in rats) with little to no negative effects. 10,11 The above-mentioned properties make C 60 fullerenes an attractive therapeutic remedy, and it is tempting to test the ability of C 60 fullerenes to prolong the lifespan of animals. However, such data are scarce and contradictory. ...
... 12 C 60 fullerenes dissolved in virgin olive oil prolonged rats' lifespan almost twice with no signs of toxicity. 10 On the contrary, Grohn et al. reported no significant effect of pristine C 60 fullerenes on mean lifespan in C57BL/6J mice in the recent article. 13 These data suggest that C 60 fullerenes may have geroprotector properties, and their use may be beneficial for health. ...
... 13 These data suggest that C 60 fullerenes may have geroprotector properties, and their use may be beneficial for health. In the present study, we repeatedly treated mature mice (10-12 months old) with C 60 fullerenes dissolved in virgin olive oil, as described in Baati et al., 10 but with a double dose (3.4 mg/kg, in contrast to 1.7 mg/kg in the original article). We analyzed the lifespan of mice, their major physiological parameters (locomotor activity, blood tests, and blood glucose level), and performed necropsies with a focus on assessing the incidence of tumors. ...
Article
Several studies claimed C60 fullerenes as a prospective geroprotector drug due to their ability to capture free radicals effectively and caused a profound interest in C60 in life extension communities. Multiple additives are already sold for human consumption despite a small body of evidence supporting the beneficial effects of fullerenes on the lifespan. In order to test the effect of C60 fullerenes on lifespan and healthspan, we administered C60 fullerenes dissolved in virgin olive oil orally to 10-12 months old CBA/Ca mice of both genders for seven months and assessed their survival. To uncover C60 and virgin olive effects, we established two control groups: mice treated with virgin olive oil (vehicle) and mice treated with drinking water. To measure healthspan, we conducted daily monitoring of health condition and lethality and monthly bodyweight measurements. We also assessed physical activity, glucose metabolism, and hematological parameters every three months. We did not observe health deterioration in the animals treated with C60 compared with the control groups. Treatment of mice with C60 fullerenes resulted in an increased lifespan of males and females compared with the olive oil-treated animals. The lifespan of C60-treated mice was similar to the mice treated with water. These results suggest that the lifespan-extending effect in C60-treated mice appears due to the protective effect of fullerenes in opposition to the negative effect of olive oil in CBA/Ca mice.
... According to the Toxicological classification of substances exhibiting toxicity at doses above 1 g/kg, belong to the class of non-toxic substances. A long experiment was conducted in rats the diet of which added fullerene in the form of solution in olive oil [16]. The experiment lasted 5.5 years, as a control diet with the addition of just olive oil and water. ...
... For example, the value for fullerenol in intraperitoneal mice is 1.2 g/kg [38,39]. Parenteral administration of the amino-acid derivative to mice at a dose of 80 mg/kg had no effect on the behavior and viability of mice for 6 months [16]. • In [12] it was shown, that water solutions of octo-adduct C 60 with arginine are characterized by acceptable (i.e., low) toxicity and the only one most concentrated solution (with concentration 0.25 g/dm 3 ) can be characterized by moderate toxicity (at the lower limit). ...
... HPLC identification of fullerene C 60 nanoparticles in the liver. High performance liquid chromatography (HPLC) is the main method for detecting fullerene C 60 in biological samples [15][16][17]. The method is based on hydrophobic interactions between fullerene molecules and the stationary C18 phase in a flow of a more hydrophilic solvent. ...
... The almost complete absence of C 60 fullerene accumulation in internal organs, despite the signifi- cant lipophilicity of this compound and its pronounced effect on a number of studied parameters, was confirmed in a number of toxicological studies [16,17,19], including 28-and 92-day oral administra-tion. With the natural (oral) intake path of C 60 , its biodegradation or biotransformation is possible, which creates additional difficulties for an accurate assessment of the C 60 content in a particular organ of a living organism. ...
Article
Fullerenes C60 are used in various fields of industry; therefore, issues of studying their biosafety for living organisms, their biodistribution in organs and tissues organs and tissues of laboratory animals, and their induction of cellular pathologies are very important. In recent years, analytical and transmission electron microscopy (TEM) have proven their efficiency in detecting carbon nanoparticles in biological samples. Combining these methods can reveal pathological changes in cells induced by nanoparticles and detect accumulations of nanoparticles in them. The aim of the study was to reveal cellular pathologies upon direct shortterm administration of fullerene C60 nanoparticles into the gastrointestinal tract (GIT) of rats and to detect nanoparticles in samples of the small intestine and liver. The histological and ultrastructural analysis did not reveal pathological changes in the small intestine, but degenerative changes in hepatocytes were indicated in the form of accumulation of lipid inclusions. High-performance liquid chromatography and analytical TEM revealed no accumulations of fullerene C60 nanoparticles in the studied samples. Probably, hepatosteatosis may be a consequence of the indirect influence of C60 nanoparticles on liver cells. Apparently, the surface of fullerene C60 undergoes modifications in the GIT, and its contact with the cells of the small intestine induces the synthesis of proinflammatory cytokines, with their subsequent entry into the liver, leading to the rapid development of fatty degeneration. Revealing and identifying modified C60 nanoparticles and their metabolites, in turn, is a complex problem, which in the future can be solved using radiotracers, mass spectrometry, and modern metabolomic technologies.
... C60 is sparingly soluble in many organic solvents [7]. To avoid toxicity, the use of biocompatible solvents, such as vegetable oils [8], is mandatory for its application in living systems [9]. The C60 solubility depends on the saturation level of vegetable oils, being higher in oils with a higher degree of unsaturated fatty acids [9]. ...
... C60 fullerene was obtained by Bucky USA, Lake Jackson, TX, USA, CAS# 99685-96-8, 99% purity. Fullerene doses were selected to reach animal daily C60 intake of about 1 mg/kg b.m. and 5 mg/kg b.m. [8]. C60 was stirred in VOO for one week at room temperature due to high insolubility, covered with aluminium foil to avoid UV irradiation [10]. ...
Article
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Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical's scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role. Citation: Ðurašević, S.; Pejić, S.; Grigorov, I.; Nikolić, G.; Mitić-Ćulafić, D.; Dragićević, M.; Ðordević, J.; Todorović Vukotić, N.; Ðordević, N.; Todorović, A.; et al. Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. Antioxidants 2021, 10, 911. https://doi.org/10.3390/antiox10060911
... To study chronic toxicity, a long experiment was conducted on rats [122], in the diet of which fullerene was added in the form of a solution in olive oil (C 60 -Olive). As a control, diets with the addition of just olive oil and water were used. ...
... The survival rate of rats (Wistar) when fed with water (control group) ( ), olive oil (Chemlali Boughrara) ( ) and a solution of fullerene C 60 in olive oil ( )[122]. ...
Article
The review discusses prospects for the use of fullerenes and their various functionalised adducts: polyhydroxylated fullerenes (fullerenols), carboxylated fullerenes, adducts with amino acids, peptides and proteins, amino adducts, glycofullerenes (“sugar balls”), adducts of fullerenes with porphyrins, as well as endometallofullerenes. The review article will be useful for specialists working in the field of nanomedicine and nanoengineering.
... The exposure to Olive oil and C 60 Fullerene were carried out with oral gavage. C 60 fullerene was dissolved in olive oil as described by Baati et al. [41] and was stored in the dark at a working concentration of 0.4 mg/ml at 4 °C. The applied C 60 fullerene dose was selected in accordance with previous studies including both hydrated C 60 and olive oil extracted C 60 fullerene [31,35,36,41]. ...
... C 60 fullerene was dissolved in olive oil as described by Baati et al. [41] and was stored in the dark at a working concentration of 0.4 mg/ml at 4 °C. The applied C 60 fullerene dose was selected in accordance with previous studies including both hydrated C 60 and olive oil extracted C 60 fullerene [31,35,36,41]. Pristine C 60 fullerene extracted with olive oil was administered 3 times per week orally at a dose of C 60 1.0 mg/kg/week throughout the 12 weeks period. ...
Article
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Diabetes mellitus is a prevalent metabolic disorder associated with multiple complications including neuropathy, memory loss and cognitive decline. Despite a long history of studies on diabetic complications, there are no effective therapeutic strategies for neuroprotection in diabetes. Hyperglycemia-induced imbalance in programmed cell death could initiate a decline in neural tissue cells viability. Various nanomaterials can induce either cell death or cell survival dependent on the type and surface features. Pristine C60 fullerene is a nontoxic nanomaterial, which exhibits antioxidant and cytoprotective properties. However, the precise molecular mechanism with which the C60 nanoparticle exerts cytoprotective effect in diabetic subjects has not yet been fully addressed. Thus, this study aimed to determine whether C60 fullerene prevents oxidative stress impairment and to explore the effects of C60 fullerene on apoptosis and autophagy in diabetes mellitus to clarify its potential mechanisms. These effects have been examined for olive oil extracted C60 fullerene on the hippocampus of STZ diabetic rats. Up-regulation of Caspase-3, Beclin-1 and oxidative stress indexes and down-regulation of Bcl-2 were observed in the brain of STZ-diabetic rats. The exposure to C60 fullerene for a period of 12 weeks ameliorate redox imbalance, hyperglycemia-induced disturbances in apoptosis and autophagy flux via modulation of Caspase-3, Bcl-2, Beclin-1 and LC3I/II contents. Furthermore, C60 fullerene ameliorated the LC3I/II ratio and prevented extremely increased autophagy flux. Contrarily, pristine C60 fullerene had no modulatory effect on all studied apoptotic and autophagy markers in non-diabetic groups. Therefore, oil extracted C60 fullerene exhibits cytoprotective effect in hyperglycemia-stressed hippocampal cells. The presented results confirm that pristine C60 fullerene nanoparticles can protect hippocampal cells against hyperglycemic stress via anti-oxidant, anti-apoptotic effects and amelioration of autophagy flux. Moreover, C60 fullerene regulates a balance of autophagy via BCL-2/Beclin-1 reciprocal expression that could prevent functional disturbances in hippocampus.
... Fullerene C 60 may be a powerful antioxidant demonstrating anti-aging activity. Recently Baati et al. showed that fullerene prolonged rat's life span approximately twice [1]. Besides, rats treated with fullerene C 60 demonstrated high resistance to carbon tetrachloride capable of triggering generation of huge amounts of harmful reactive oxygen species. ...
... Consequently, fullerene C 60 was proposed to have high antioxidant activity in vivo. Geroprotective activity of C 60 fullerene found experimentally in [1] is much higher than those of the most powerful reactive oxygen species scavengers. ...
Article
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Fullerene C60 compound was recently found to be a potent anti-oxidant, which may be envisioned as a result of alteration of the inner mitohondria membrane electric potential with protons transport boosted by fullerenes. Here we briefly report on the theoretical test of the very possibility of protons to pass through the surface of C60 fullerene to become confined within latter thus possibly decreasing the transmembrane electric field gradient when fullerene crosses the mitochondria membrane. Quantumchemical calculations within Density Functional Theory are employed as a means of checking described scenario
... It should be taken into account that the growing market on pristine and functionalized fullerenes in combination with their potential to direct human exposure through multiple applications, especially biomedial ones, has led to widespread concerns about their probable adverse effects on human health. However, their effects on humans, as well as in the environment, are yet poorly understood and contradictory reports on their hazard can be found in the literature [12][13][14][15][16][17][18][19]. For example, Waissi-Leinonen et al. [12] studied the toxicity of C60 fullerene to sediment-dwelling invertebrate Chironomus riparius larvae, and observed that in the organisms exposed to fullerenes, microvilli were damaged and were significantly shorter, concluding that the potential toxicity of fullerene to C. riparius appeared to be caused by morphological changes, inhibiting larval growth. ...
... Only minor changes were observed and only in one animal, and no clinically significant chemistry changes were reported, suggesting that this fullerol seemed to be well tolerated after iv administration to rats. In another work, Baati et al. [13] showed that administration of C60 dissolved in olive oil (0.8 mg/mL) at reiterated doses (1.7 mg/kg of body weight) to rats not only did not entail chronic toxicity but it almost doubled their lifespan. This effect was mainly attributed to the attenuation of age-associated increases in oxidative stress. ...
Chapter
The nanotechnology era was born with the first synthesis of carbon-based nanomaterials (carbon nanoparticles, CNPs), C60 fullerene (Buckminster fullerene, or Bucky ball), by Professor Kroto and collaborators in the 1980s. The discovery of fullerenes by the laser vaporization technique resulted in the award of Chemistry Nobel Prize to Curl, Kroto, and Smalley in 1996. Fullerenes have been studied in depth because of their unique structure and potential as new nanomaterials. This is due to their appealing photo-, electro-chemical, and physical properties, which make them exploitable in different fields, such as biomedical, cosmetic and industrial applications, ranging from drug-delivery systems and anti-aging formulations to electrical components. The rapid growth in the development, production, and use of these compounds over the last years increased their dispersion in the environment. Moreover, their unique colloidal properties in water can affect their behavior in the environment. For instance, although C60 is practically insoluble in water, it can spontaneously form stable aqueous colloidal suspensions containing nanocrystalline aggregates with effective aqueous phase concentrations many orders of magnitude above that corresponding to the aqueous solubility of molecular fullerenes. Consequently, the ability of these carbon nanomaterials to form aggregates could change their bioavailability, leading to additional toxicological concerns, although at the moment data regarding their toxicity is limited. Although significant advances have been made in the analysis of fullerenes in the past few years, there is still an increasing need to develop effective, sensitive, and reliable analytical methods for their determination. Liquid chromatography with UV-detection (LC-UV) or coupled with mass spectrometry (LC-MS) or high-resolution mass spectrometry (LC-HRMS) are among the most effective methods for their determination in environmental samples. This chapter aims to review the role of liquid chromatography techniques in the analysis of fullerenes, and to assess the occurrence of this family of compounds in the environment. Coverage of all kind of applications is beyond the scope of the present contribution, so the chapter will focus on the most relevant applications published in the last years.
... After sourcing the high purity C 60 , we prepared C 60 -olive oil solution according to Batti et al.(2012). Fifty mg of C 60 was dissolved in 10 ml of olive oil by stirring for 2 weeks at ambient temperature in the dark. ...
... Limited research such as Baati., et al. report enhanced longevity, along with the retention of more youthful characteristics in energy and appearance [27]. ...
Article
Full-text available
Fullerene materials are often reported to be excellent antioxidants in cells. Usually, direct free radical scavenging mechanisms, as seen in polymer and food industry research, is the proposed antioxidant mechanism. However, free radical scavenging by antioxidants in vivo is kinetically unlikely and conflicts with the molecular properties of fullerene materials. Pristine fullerene materials, and many of their derivatives, have pro-oxidant properties and form adducts, which are both potentially toxic mechanisms in vivo. Although they are electrophilic with an affinity for electrons, they appear to function similarly to other non-radical electrophilic antioxidants that stimulate enzymatic oxidative stress management and protection through Nrf-2 pathways. We approach the antioxidant role of fullerene materials from the perspective that they do not act as direct free radical scavengers. Other mechanisms have been previously proposed that are more consistent with fullerene properties and antioxidant benefits in vivo. Here we discuss fullerene materials as electron scavenging antioxidants rather than free radical scavengers. We propose that fullerene materials scavenge excess electrons in the electron transport chain, preventing the formation of superoxide and hydroxyl radicals in the mitochondria. The scavenging of electrons would assist in preventing damage to mitochondrial structures and DNA, maintaining optimum oxidized to reduced nicotinamide adenine dinucleotide (NAD+/NADH) ratios, as well as in maintaining an oxidized respiratory enzyme system in mitochondrial conditions resulting from excess caloric intake in the absence of cellular energy requirements and progressive mitochondrial dysfunction related to oxidative stress. Further research is needed to evaluate the utilization of fullerene materials for use in metabolic syndromes and neurodegenerative conditions that may be complicated by progressive mitochondrial oxidative damage.
... In addition, an aqueous dispersion of fullerene C 60 (socalled aqu/nC 60 ) can be obtained relatively easily by slowly evaporating the organic component of the solvent with the gradual addition in small quantities of distilled water into the C 60 solution [14,15,16], as well as by popular method based on the functionalization of fullerene molecules such as the formation of fullerenol [17,18]. The aqueous dispersions of C 60 retain their structural stability for 3-4 months [19] and find the most important practical application in medicine as powerful antiviral [20,21,22] and anti-allergic drugs [23,24], drugs for the fight against cancer [25,26], as well as in substances that stimulate the immune system [27,28], as a powerful antioxidant [29,30], to protect the brain from alcohol [31,32], to stimulate hair growth [33,34], to protect the body from radiation and ultraviolet radiation [35,36,37], to slow down aging [38,39] and others. ...
Article
Full-text available
The experimental results on the self-aggregation of fullerene C60 particles in a microvolume of drying droplets of a colloidal solution of fullerene on a solid substrate are presented. Using methods of scanning electron microscopy and atomic force microscopy, it was shown that in the volume of an evaporating droplet of a solution of fullerene C60 in xylene, deposited on the surface of a flat silicon substrate at room temperature, nanostructured and porous mC60 aggregates of quasispherical and elongated spherical shapes with geometrical sizes in average diameter up to D ≈ 4000 nm are synthesized. It is established that an increase in the fullerene concentration in the initial drop of the same solution leads to an increase in the average size of the resulting fullerene aggregates. The basic physical features and regularities characterizing the processes of self-aggregation of fullerene particles in a volume of drying drop were determined.
... 39 Fullerene (C 60 ) has been dissolved into olive oil and administered repeatedly with a certain dose into rats and shown that there are no toxicity dangers and, in fact, it doubled the lifespan of the rats. 40 Furthermore, olive oil has a protective role as a solvent for iron oxide nanoparticles when administered into male albino rats. 41 Hence, it is clear that the use of nanomaterials in olive oil may provide significant future biomedical applications. ...
... Some of these compounds have indeed displayed the beneficial medical effects, among them antioxidant properties and neuroprotective effects, healing tendencies against hepatitis C, antibacterial and anti-viral properties, even anti-HIV. There are the evidences regarding prospects of the fullerene derivatives in oncology and anti-aging medicine [2,[5][6][7][8][9][10][11][12][13][14][15]. Some fullerenes, under the action of UV light, produce singlet oxygen and other reactive oxygen species and, thus, they can be used, for example, in the photodynamic therapy of cancer. ...
Article
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Opinion Fullerenes are the third allotropic form of carbon, along with diamond and graphite, where carbon atoms are situated in vertices of the closed shells (cages) [1]. Since their discovery in 1985, fullerenes have attracted an attention of scientists not only because of their unique and beautiful structure but also as the materials for possible applications in engineering and medicine. Lots of fullerenes with hollow carbon cages were synthesized and chemically functionalized. Biomedical effects of such "empty" fullerenes are mostly defined by the chemical groups attached to the fullerene cage [1,2]. Besides, there are the so-called endohedral metallofullerenes (EMF) molecules of which contain one or more atoms, among them lanthanides or heavy elements like Pb or Bi trapped inside the carbon cage [3,4]. The goal of this editorial is to summarize the ideas of using fullerenes for biomedicine and express our opinion concerning the prospects of their application for therapeutic purposes. The discovery of fullerenes has inspired the searching of novel fullerene-based drugs. Over the last three and a half decades, lots of so-called chemically functionalized fullerenes, with carbon cages containing up to 132 carbon atoms, were synthesized and tested in biomedical experiments. Some of these compounds have indeed displayed the beneficial medical effects, among them antioxidant properties and neuroprotective effects, healing tendencies against hepatitis C, antibacterial and anti-viral properties, even anti-HIV. There are the evidences regarding prospects of the fullerene derivatives in oncology and anti-aging medicine [2,5-15]. Some fullerenes, under the action of UV light, produce singlet oxygen and other reactive oxygen species and, thus, they can be used, for example, in the photodynamic therapy of cancer. Moreover, the beneficial effects of the fullerene derivatives against diabetes (type 2 diabetes mellitus) and Alzheimer disease were revealed in the experiments with rats [14,15]. Usual laboratory Wistar rats do not suffer from Diabetes Type II or Alzheimer disease, but the fullerene enthusiasm has apparently brought the Russian scientists out of the routine knowledge. Endohedral metallofullerenes also appear to have a considerable promise in biomedicine. It has been suggested that EMF with the appropriate particle-emitting radionuclides inside, among them β-emitting 89 Sr, 90 Y, 47 Sc, 64 Cu, 149 Pr, 153 Sm, 166 Ho, and 177 Lu show promise for radiation medicine while the advances in the molecular biotechnology provide targeting vectors to deliver therapeutic doses of the ionizing radiation with high specificity to the metastatic cancer cells thereby decreasing irradiation of healthy tissues [16]. Recently, the radioactive Pb-EMF and Bi-EMF, with β-emitting 212 Pb and α-emitting 212 Bi inside the cage, and there malonic ester derivatives were prepared for the first time [17]. The anti-cancer effects of 212 Pb, despite the favorable decay characteristics of this radionuclide, are usually limited because of the myelotoxicity resulting from accumulation of 212 Pb in the bone marrow. In the experiments with mice it was found that 212 Pb did not accumulate in the bone marrow after being administered within the endohedral fullerene, in contrast to the results with conventional poly amino carboxylate chelators for 212 Pb. The EMF molecules encapsulate radionuclides more stably and, thus, could potentially play a valuable role in radioimmunotherapy [17].
... The procedure described by (Baati et al., 2012) was implemented for dissolving C60 in olive oil after which it was stored in the dark at a working concentration of 0.4 mg/ml at 4°C (Aly, Kotb, Haridy, & Hammad, 2018). CUR was also dissolved in olive oil and stored in the dark and working concentration of 10 mg/ml at 4°C (Abdel Aziz et al., 2012). ...
Article
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The present study aims to examine the protective effects of C60 fullerene (C60), Curcumin (CUR; Curcuma longa), C60 + CUR combination against oxidative stress, apoptosis, and changes in cellular level in kidney tissue of diabetic rats. Treatment practices were administered separately to groups for 8 weeks following the approval of diabetes induction. It was observed that the treatment groups had increased antioxidant potential, decreased oxidative stress levels, decreased cholesterol, alpha tocopherol, retinol levels along with improved important changes in fatty acid metabolism compared with the diabetic group. C60, CUR, and C60 + CUR were also determined to act in the direction of reducing kidney damage by activating apoptotic pathways. It can be concluded based on these findings that C60, CUR, and especially C60 + CUR combination has beneficial properties in maintaining kidney tissue and function by effectively preventing oxidative stress, apoptotic changes, and changes at the cellular level in kidney tissue under hyperglycemia conditions. Practical applications C60 and CUR have various biological activities which can be indicated as antioxidant, anti‐inflammatory, anticancer, neuroprotective, and hepatoprotective. It has been reported that C60 and CUR protect the cells against oxidative injury brought about by reactive oxygen species (ROS). Data acquired from the present study puts forth that C60 and C60 + CUR may be promising agents to prevent damage induced by hyperglycemic conditions in kidney tissue.
... After administering the fullerene materials to the rodents (the fullerene material had been dissolved in olive oil), no signs of toxicity or tumor recurrence were observed, even after the fullerenes were reinforced with photodynamic energy. The rats showed improved immune responses and general long-term beneficial effects as tumors were eradicated [23,27]. ...
Article
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Carbon fullerene materials have been investigated for applications in humans for nearly fifty years. Fullerene materials are composed of carbon atoms and are compatible with specific biological systems. They reduce the number of free radicals in cells, provide anti-inflammatory effects, and inhibit tumor growth. However, the primary antioxidant benefit of fullerene materials seems to be the activation of nuclear factor (erythroid-derived 2) factor 2 (Nrf2). Nanocarbon onion-like fullerene (NOLF) materials have a high surface area to volume ratio, making them viable for transportation within humans and animals. They aid in targeted drug delivery for varying conditions, such as cancer therapy. However, NOLFs safety, manufacture, and dosage should be further evaluated for consistency and toxicity and established for the safe therapeutic use in humans, animals, and plants.
... Fullerene molecules were introduced in olive oil to test the longevity properties of the carbon allotrope materials [27]. Oral administration of fullerene materials dissolved in the olive oil demonstrated longevity in experimental rats [34,35]. Also, the intoxication of CCl4 in the rats was prevented by nanocarbon fullerene materials applied over extended periods [36]. ...
Article
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Since the 1980s, carbon fullerene materials have been investigated for applications in humans and animals [1]. Fullerene materials are composed of carbon atoms and are compatible with biological systems in vertebrates. They reduce free radicals in cells, provide anti-inflammatory effects, and inhibit tumor growth. However, the primary antioxidant benefit of fullerene materials might be the activation of nuclear factor (erythroid-derived 2) factor 2 (Nrf2). Nanocarbon onion-like fullerene (NOLF) materials have a high surface area to volume ratio, making them viable for transportation within humans and animals. They aid in targeted drug delivery systems for varying conditions, such as cancer therapy. However, NOLFs safety, manufacture, and dosage should be further evaluated and established for their therapeutic use in humans and animals [2].
... Administration of fullerene during ischemic stroke decreased the injuries of cerebral ischemia by inhibition of oxidative damage and inflammation (17)(18)(19). Furthermore, repeated oral administration of fullerene C60 prolonged the lifespan in CCl4-mediated toxicity in rats (12). ...
... Nanocarbon fullerenes have been applied in animals to enhance longevity, eliminate tumors, and improve fertility, increasing productivity and profits over time [16]. They reduce the number of free radicals in cells [17][18][19][20], provide anti-inflammatory effects [17,19], and inhibit tumor growth [21][22][23][24]. However, the primary antioxidant benefit of fullerene materials seems to be the activation of nuclear factor (erythroid-derived 2) factor 2 (Nrf2) [25,26]. ...
Article
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Carbon fullerene materials have been investigated for applications in humans, animals, and plants for decades. Fullerene materials are composed of carbon atoms and are compatible with specific biological systems, while showing little to no toxicity. They reduce the number of free radicals in cells, provide anti-inflammatory effects, and inhibit tumor growth. However, the primary antioxidant benefit of fullerene materials seems to be the activation of nuclear factor (erythroid-derived 2) factor 2 (Nrf2). Their application can enhance productivity and improve crop yield by stimulating water retention and fighting specific disease organisms in agriculture. Their application in husbandry can enhance productivity and profitability, in part, by stimulating metabolism and immunity. Nano-carbon onion-like fullerene (NOLF) materials have a high surface area to volume ratio, making them viable for transportation within biologic systems. However, NOLFs safety, manufacture, and dosage should be further evaluated for consistency and toxicity, and established for the safe use in humans, animals, and plants.
... C 60 is chemically versatile, and many synthetic strategies of derivatization have already been developed [10][11][12][13][14][15][16], which provides great flexibility when designing a C 60 engrafted with therapeutics. Inherently, C 60 has also shown strong antioxidant behavior through its ability to quench free radicals [17,18] and has been observed to nearly double the lifespan of rodents, presumably because of this radical-scavenging property [19,20]. Conversely, certain C 60 derivatives can generate reactive oxygen species under light irradiation, allowing these derivatives to be used for photodynamic therapy (PDT) against cancer [21,22]. ...
Article
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Carbon nanoparticles have consistently been of great interest in medicine. However, there are currently no clinical materials based on carbon nanoparticles, due to inconsistent biodistribution and excretion data. In this work, we have synthesized a novel C60 derivative with a metal chelating agent (NOTA) covalently bound to the C60 cage and radiolabeled with copper-64 (t1/2 = 12.7 h). Biodistribution of the material was assessed in vivo using positron emission tomography (PET). Bingel-Hirsch chemistry was employed to functionalize the fullerene cage with highly water-soluble serinolamide groups allowing this new C60 conjugate to clear quickly from mice almost exclusively through the kidneys. Comparing the present results to the larger context of reports of biocompatible fullerene derivatives, this work offers an important evaluation of the in vivo biodistribution, using experimental evidence to establish functionalization guidelines for future C60-based biomedical platforms.
... 10 Studies have shown that the carbon 60 dissolved in vegetable oils is a powerful antioxidant that has various therapeutic effects; the oral administration of C60 dissolved in olive oil in repeated doses to rats not only does not entail chronic toxicity but almost doubles their life expectancy in these animals. 11 In previous results obtained in our laboratory, soon to be published, the pharmacological potential of C60 dissolved in grape seed oil (C60-Oil) as an anti-inflammatory and antioxidant is demonstrated. C60-Oil inhibits the release of TNF-α, the migration and production of ROS by human neutrophils; it also has a significant scavenging effect on superoxide free radicals and DPPH free radicals, and oral administration of C60-Oil strongly reduced the serum C-Reactive Protein (CRP) in dogs. ...
Article
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Introduction: Carbon 60 (C60) and its derivatives have various biological applications. In our laboratory, we have demonstrated that C60 dissolved in grape seed oil (C60-Oil) has antioxidant and anti-inflammatory properties; however, the effectiveness of this formulation to treat diseases of the intestinal tract and specifically ulcerative colitis has not been studied. In this study, we intend to explore the effects of C60-Oil against experimental ulcerative colitis induced by Dextran Sulfate Sodium (DSS) in rats and a human colorectal cell line, HT-29. Methods: The rats were randomly distributed into three groups: a negative control group with no induced damage and two other groups were treated with DSS to induce UC for seven days: one as untreated control and the other group treated with C60-Oil 3 mg/kg/day. We quantified the clinical manifestations of the disease, body weight, colon weight, microscopic damage score, and colonic content of IL-6, TNF-alpha, IL-1B, and IL-10. As part of the cell studies, HT-29 cells were pretreated with C60-Oil at different concentrations (0.1, 1, 5, 10, 50, 30 μg/mL) and then stimulated with DSS (10 μg/mL). We measured the levels of IL-8 and NO secreted in the medium and the intracellular levels of ROS. Results: Oral treatment with C60-Oil significantly prevented the change in body weight, reduced most of the clinical signs of the disease, colon weight, microscopic damage score, and considerably improved the profile of cytokines analyzed. The pretreatment of HT-29 cells also protected the cells from the action of DSS as it reduced the levels of IL-8, NO, and ROS. Conclusion: According to our results, we can suggest C60-Oil, as a formulation with pharmacological potential for treating ulcerative colitis.
... The procedure set forth by (Baati et al. 2012) was applied for dissolving C60 in olive oil after which it was stored in the dark at a working concentration of 0.4 mg/ml at 4°C (Aly et al. 2018). Cur was also dissolved in olive oil after which it was stored in the dark at a working concentration of 10 mg/ml at 4°C (Abdel Aziz et al. 2012). ...
Article
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Increasing evidence suggests that diabetes also targets lung tissues resulting in structural and physiological abnormalities. The present study evaluated the impact of pristine C60 fullerene (C60) against diabetes-induced lung damage for the first time. The objective was to evaluate the impacts of Curcumin (Cur), C60 and C60 fullerene+Curcumin (C60 + Cur) combination on oxidative stress (MDA, GSH, CAT, GST, Retinol, α-tocopherol), apoptosis (Caspase-3, Bcl-2), cholesterol and fatty acid profile (16:0,18:0,18:1,18:2, 22:4, 22:6) against changes in the lung tissue of diabetic rats. Streptozotocin (STZ) was used for inducing diabetes with Cur, C60 and C60 + Cur combination administered for eight weeks to treat diabetic and control rats. Increased oxidative stress, apoptosis and significant changes in cell structure were observed in the lung tissues of diabetic rats. The combination of Cur, C60 and C60 + Cur reduced oxidative stress in the lung tissue of diabetic rats while increasing the antioxidant defense capacity of the tissue, exhibiting tissue protective properties against apoptosis. The diabetic rats displayed favorable properties against lipotoxicity-induced tissue damage due to the increase in the fatty acid and cholesterol levels in lung tissue. It was observed that Cur, C60 and C60 + Cur combination displays protective effects against hyperglycemia induced oxidative damage to lung tissue. Oxidative stress, prevention of lipid and cholesterol accumulation, and weakening of lung apoptosis may be associated with these effects.
... Fullerene C60 derivatives also improve oxidative stress and decrease cell cytotoxicity developed by photo (13). So, daily and long-term treatment with fullerene C60 nanoparticles prolongs survival in an experimental model of CCl4 intoxication in rats (14). Likewise, the neuroprotective activity of fullerene C60 against cerebral ischemia/reperfusion injuries has been demonstrated through improving oxidative stress damage (15). ...
Article
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Background & Objective: Occurrence of oxidative stress in uncontrolled diabetes mellitus affects spermatogenesis and testicular functions. As the promising antioxidant activities of fullerene C60 nanomaterial have been demonstrated by previous reports, the current study aimed to determine its effects on the markers of oxidative stress damage in streptozotocin-induced diabetes testes in rats. Materials & Methods: To perform the current study, 32 male Wistar rats were assigned to four groups (each group, n=8) as follows: two control (normal and diabetic) and two treated (normal and diabetic) groups. Streptozotocin at dose of 45 mg/kg (i.v. injection) was used to induce diabetes at the beginning of the test. Treated rats orally received fullerene C60 (1 mg/kg/day) for 8 weeks. The markers of oxidative stress damage were assessed in the testes at the end of the study, including malondialdehyde (MDA) and glutathione (GSH) contents as well as superoxide dismutase (SOD) and catalase (CAT) activities. One-way ANOVA and Tukey’s post-hoc test were used to analyze the data. Results: Blood glucose level was not altered in the fullerene-treated normal and diabetic animals. Diabetes induction increased MDA level, but decreased CAT activity in the testes of diabetic animals compared to the normal animals. Administering fullerene C60 significantly decreased MDA content and increased the activity of CAT in the testes of diabetic animals compared to the untreated diabetic rats. Fullerene C60 administration in normal animals also decreased the activity of SOD in the testes. Conclusion: According to our findings, fullerene C60 nanoparticles could reduce oxidative stress damage in diabetic condition in rat testicular tissue probably through potentiating the antioxidant defense system. © 2020, Zanjan University of Medical Sciences and Health Services. All rights reserved.
... 21 Many concerns and debates among the society, industry, and regulatory authorities (i.e., REACH or European Community Regulation on chemicals) are regarding the safety of nanoparticles and their final fate in biological systems. 22,23 Toxicity of novel purely inorganic nanoparticles such as fullerenes 24 and carbon nanotubes (CNTs) 25 (quantum dots, 26 silica, 27 and iron oxides 28 ) is not fully understood. Hence, prior to any practical use of nanoparticles particularly for biomedical applications, it is of a high societal relevance to investigate their possible toxic effects. ...
Article
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Titanate nanotubes (TiNTs) produced by the static hydrothermal process present a promising nanosystem for nanomedicine. However, the behavior of these nanotubes in vivo is not yet clarified. In this work, for the first time, we investigated the toxicity of these materials, their pharmacokinetic profile, and their biodistribution in mice. A high dose of TiNTs (45 mg/kg) was intravenously injected in mice and monitored from 6 h to 45 days. The histological examination of organs and the analysis of liver and kidney function markers and then the inflammatory response were in agreement with a long-term innocuity of these nanomaterials. The parameters of pharmacokinetics revealed the rapid clarification of TiNTs from the bloodstream after 6 h of the intravenous injection which then mainly accumulated in the liver and spleen, and their degradation and clearance in these tissues were relatively slow (>4 weeks). Interestingly, an important property of these materials is their slow dissolution under the lysosome acid environment, rendering them biodegradable. It is noteworthy that TiNTs were directly eliminated in urine and bile ducts without obvious toxicity in mice. Altogether, all these typical in vivo tests studying the TiNT pharmacokinetics, toxicity, and biodistribution are supporting the use of these biocompatible nanomaterials in the biomedical field, especially as a nanocarrier-based drug delivery system.
... Since in biological systems reactions with the participation of free radicals are mainly oxidation reactions, then one of the biological properties of fullerene C 60 can be antioxidant activity [26][27][28][29][30] . In ref. 31 , results were obtained OPEN 1 Pavlov First Saint Petersburg State Medical University, L'va Tolstogo ulitsa 6-8, Saint Petersburg, ...
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The article is devoted to the study of the pharmacokinetics of fullerene C60 in oil and micellar forms, analysis of its content in blood, liver, lungs, kidneys, heart, brain, adrenal glands, thymus, testicles, and spleen. The highest accumulation of C60 was found in the liver and adrenal glands. As a result of the studies carried out, it was shown that the bioavailability of C60 in the micellar form is higher than that in an oil solution.
... The application of new nanoscale structures in biological systems needs chemical and biological compatibility appropriate for the desired point [30]. In vivo biomedical usage of nanomaterials requests low toxicity, low immunogenicity, and ultimate clearance. ...
... Since fullerene family was discovered at the end of last century, many important aspects on these molecules have been accumulated to form a new scientific field. The hydrophobicity, three-dimensionality, nano size and electronic configuration make them an appealing subject in different areas (Liu et al. 2013;Perezet al. 2013;Thilgen et al. 2006)especially in biology and medicine (Baati et al. 2012;Ma et al. 2010;Theriot et al. 2010;Bobylev et al. 2011;Meng et al. 2010;Xu et al. 2011;Tsumoto et al. 2010). However, the difficult processibility of fullerenes has led to the developments of methods for the functionalization of them. ...
... Fullerene is a stronger antioxidant with anti-aging properties. Recently, Baati et al. [51] showed that the repeated oral administration of fullerene (in olive oil) in rats doubled their lifespan without causing chronic toxicity. However, a lower water solubility limited the medical applications of fullerene. ...
Article
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Particulate matter (PM), a widespread air pollutant, consists of a complex mixture of solid and liquid particles suspended in air. Many diseases have been linked to PM exposure, which induces an imbalance in reactive oxygen species (ROS) generated in cells, and might result in skin diseases (such as aging and atopic dermatitis). New techniques involving nanomedicine and nano-delivery systems are being rapidly developed in the medicinal field. Fullerene, a kind of nanomaterial, acts as a super radical scavenger. Lower water solubility levels limit the bio-applications of fullerene. Hence, to improve the water solubility of fullerene, while retaining its radical scavenger functions, a fullerene derivative, fullerenol C60(OH)36, was synthesized, to examine its biofunctions in PM-exposed human keratinocyte (HaCaT) cells. The PM-induced increase in ROS levels and expression of phosphorylated mitogen-activated protein kinase and Akt could be inhibited via fullerenol pre-treatment. Furthermore, the expression of inflammation-related proteins, cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2 was also suppressed. Fullerenol could preserve the impaired state of skin barrier proteins (filaggrin, involucrin, repetin, and loricrin), which was attributable to PM exposure. These results suggest that fullerenol could act against PM-induced cytotoxicity via ROS scavenging and anti-inflammatory mechanisms, and the maintenance of expression of barrier proteins, and is a potential candidate compound for the treatment of skin diseases.
... Antioxidant activity of C 60 was shown in vitro, in vivo and in the clinical studies (Chen et al., 2004;Gharbi et al., 2005;Inui et al., 2011). Since oxidative stress is the cause and/or mechanism of many diseases, C 60 's antioxidant activity determines its strong anti-aging (Gao et al., 2011;Baati et al., 2012), antiinflammatory (Ryan et al., 2007;Dellinger et al., 2015), cardiovascular- (Thompson et al., 2014) and neuro-protective (Lee et al., 2011;Tong et al., 2011) effects. ...
Thesis
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Recent progress in nanotechnology has attracted interest to a biomedical application of the carbon nanoparticle C60 fullerene (C60) due to its unique structure and versatile biological activity. In the current study the dual functionality of C60 as a photosensitizer and a drug nanocarrier was exploited to improve the efficiency of chemotherapeutic drugs towards human leukemic cells. Pristine C60 demonstrated time-dependent accumulation with predominant mitochondrial localization in leukemic cells. C60’s effects on leukemic cells irradiated with high power single chip LEDs of different wavelengths were assessed to find out the most effective photoexcitation conditions. A C60-based noncovalent nanosized system as a carrier for an optimized drug delivery to the cells was evaluated in accordance to its physicochemical properties and toxic effects. Finally, nanomolar amounts of C60-drug nanocomplexes in 1:1 and 2:1 molar ratios were explored to improve the efficiency of cell treatment, complementing it with photodynamic approach. A proposed treatment strategy was developed for C60 nanocomplexes with the common chemotherapeutic drug Doxorubicin, whose intracellular accumulation and localization, cytotoxicity and mechanism of action were investigated. The developed strategy was revealed to be transferable to an alternative potent anticancer drug – the herbal alkaloid Berberine. Hereafter, a strong synergy of treatments arising from the combination of C60-mediated drug delivery and C60 photoexcitation was revealed. Presented data indicate that a combination of chemo- and photodynamic treatments with C60-drug nanoformulations could provide a promising synergetic approach for cancer treatment.
... The reports about the possible toxicities are controversial. Some believe that at least in physiological conditions, it seems to have no or minimal acute or subacute adverse effect both in-vitro and invivo [46,47]. An in-vitro study by Prylutska et al. showed that Nano-C60 accumulation in aqueous water did not have a toxic impact on lymphocytes' genome [47][48][49][50]. ...
Article
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Background : The distribution of drugs could not be controlled in the conventional delivery systems. This has led to the developing of a specific delivery system, called smart drug delivery systems. In cancer therapy, innovative biocompatible nanocarriers have received much attention for various ranges of anti-cancer drugs. In this work, the effect of an interesting and novel copolymer named "dimethyl acrylamide-trimethyl chitosan" was investigated on delivery of paclitaxel and doxorubicin applying carboxylated fullerene nanohybrid. The current study was run via molecular dynamics simulation and quantum calculations based on the acidic pH differences between cancerous microenvironment and normal tissues. Furthermore, hydrogen bonds, radius of gyration, and nanoparticle interaction energies were studied here. Stimulatingly, a simultaneous pH and temperature-responsive system were proposed for paclitaxel and doxorubicin for a co- polymer. A pH-responsive and thermal responsive copolymer were utilized based on trimethyl chitosan and dimethyl acrylamide, respectively. In such a dualistic approach, co-polymer makes an excellent system to possess two simultaneous properties in one bio-polymer. Results: The simulation results proposed dramatic and indisputable effects of the copolymer in the release of drugs in cancerous tissues, as well as increased biocompatibility and drug uptake in healthy tissues. Repeated simulations of a similar article performed for the validation test. The results are very close to those of the reference paper . Conclusions : Overall, conjugated modified fullerene and dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) as nanohybrid can be an appropriate proposition for drug loading, drug delivery, and drug release on dual responsive smart drug delivery system.
... The [60]fullerene molecule has a diameter of circa 1 nm, so it truly bridges the gap between molecules and nanoparticles. In the past 35 years, [60]fullerenes have been investigated for many biomedical applications by others (Berger et al. 2011;Baati et al. 2012) and ourselves (Lee et al. 2009;Cho M et al. 2010;Brame et al. 2014). The greatest difficulty in using [60]fullerene for medical applications is its inherent lipophilicity. ...
Article
Purpose: The excellent contrast of high atomic number (Z) elements compared to soft tissues has advanced their use as contrast agents for computed tomographic imaging and as potential radiation sensitizers. We evaluated whether gadolinium (Gd) could serve as such a theranostic agent for high-resolution magnetic resonance imaging (MRI) due to its paramagnetic properties and radiosensitization due to its high Z. Materials and methods: To improve the relaxivity of Gd, we coupled it to [60]fullerene, an elemental carbon allotropic nanoparticle that seamlessly traverses physiological barriers . By adding serinol, an aliphatic alcohol derived from amino acid serine, we turned [60]fullerene, which is otherwise insoluble in water, into a highly water-soluble derivative and decorated it externally with a payload of chelated gadolinium ions. Results: When [60]fullerene was functionalized in this manner with two gadolinium ions (Gd2C60), it displayed considerably higher T1 relaxivity at 4.7T than the commercially used MRI contrast agent, Magnevist, (18.2 mM⁻¹s⁻¹ vs. 4.7 mM⁻¹s⁻¹). Attempts to increase this even further via decoration of [60]fullerene with 12 gadolinium ions was unsuccessful due to a poor water solubility. However, the current formulation of Gd2C60 did not result in any appreciable radiosensitization. Conclusion: Our results show a successful generation of a novel contrast agent via decoration of fullerene with two chelated Gd ions. Though this formulation was not successful in generating radiosensitization, other chemical modifications can be further explored to increase radiosensitization potential.
... Световая микроскопия. цах [16][17][18]. Метод основан на гидрофобных взаимодействиях молекул фуллерена с неподвижной С18-фазой в потоке более гидрофильного растворителя. Проточное детектирование фуллерена осуществляется по его оптической плотности при длине волны 340 нм. ...
Article
Фуллерены С60 применяются в различных областях промышленности, в связи с чем актуальны вопросы изучения их биобезопасности для живых организмов, биораспределения по органам и тканям лабораторных животных и индукции ими клеточных патологий. В последние годы эффективность в выявлении углеродных наночастиц в биологических образцах показали методы аналитической и трансмиссионной электронной микроскопии (ТЭМ). Комбинация этих методов позволяет выявить индуцируемые наночастицами патологические изменения в клетках и детектировать в них скопления наночастиц. Целью работы было выявить клеточные патологии при прямом краткосрочном введении наночастиц фуллерена С60 в желудочно-кишечный тракт (ЖКТ) крыс и провести детекцию наночастиц в образцах тонкой кишки и печени. Гистологический и ультраструктурный анализ не выявил патологических изменений в тонкой кишке, но были показаны дистрофические изменения гепатоцитов в виде накопления липидных включений. Методы высокоэффективной жидкостной хроматографии и аналитической ТЭМ не выявили скоплений наночастиц фуллерена С60 в исследуемых образцах. Вероятно, гепатостеатоз может являться следствием непрямого воздействия наночастиц С60 на клетки печени. По-видимому, в ЖКТ происходит модификация поверхности фуллерена С60 и его контакт с клетками тонкого кишечника индуцирует синтез провоспалительных цитокинов с их последующим попаданием в печень, приводя к быстрому развитию жировой дистрофии. Выявление и идентификация модифицированных наночастиц С60 и их метаболитов, в свою очередь, являются сложной задачей, которая в перспективе может быть решена с использованием метода меченых атомов, масс-спектрометрии и современных метаболомных технологий.
Article
Abstarct The enormous potential of biosensors in medical diagnostics has motivated scientists to develop newer innovative tools and advance biosensing technologies. The use of cell, organelles, nucleotides, aptamers, antibodies, affibodies, proteins, peptides, molecules, and printed polymers, merged with nanotechnology, offers excellent tools to prepare highly sensitive and advanced biosensors. Therefore, the current decade has witnessed a rapid surge in the fabrication of different nanomaterial‐based biosensors. Among them, carbon nanomaterials (CNMs) have emerged highly attractive in the fabrication of both electrochemical and electrochemiluminescence (ECL) biosensors. On one hand, CNMs bear prominent electrical conductivity, large surface area to immobilize adequate amount of biomolecules, an enhanced loading capacity, improved biocompatibility, and active site for electrochemical reaction. Additionally, CNMs could be chemically modified for the covalent coupling with the biomolecules. On the other hand, both electrochemical and ECL biosensors allow for cost‐effective, rapid, and real‐time detection with excellent sensitivity and selectivity, with the capability of integrating different biomolecules and CNMs on the same chip. However, currently there is not a single review, which includes CNM‐based electrochemical and ECL biosensors' current progress and trends. Therefore, this review intends to survey the current progress and future trends in CNM‐based electrochemical and ECL biosensors.
Thesis
En 1985 Kroto décrit le troisième allotrope du carbone, le fullerène, une sphère de 60 carbones d’1nm de diamètre aux caractéristiques physico-chimiques particulières. La réactivité chimique du C₆₀ est dominée par les réactions d’addition et sa grande affinité pour les radicaux libres grâce à ses 30 double-liaisons. Cette propriété a été explorée dans le stress oxydant, tant in vitro qu’in vivo, où l’équilibre redox est impliqué, comme dans les situations pathophysiologiques impliquant l’inflammation et la dégénérescence cellulaire. En particulier, un traitement au C₆₀ solubilisé dans de l’huile a permis de prolonger l’espérance de vie chez le rat. Le produit, commercialisé à travers le monde, n’a pas encore fait l’objet d’essai clinique. D’autre part certaines préparations peuvent contenir des impuretés. Il est donc important d’établir des critères de pureté et d’intégrité des préparations de C₆₀. Ce travail de thèse comporte deux parties. La première, physicochimique, nous a permis d’évaluer la pureté de préparations commerciales de C₆₀ de différentes origines faisant appel à différentes techniques d’analyse: microscopie électronique à balayage, diffraction aux rayons X, calorimétrie différentielle à balayage (DSC), analyse thermogravimétrique, chromatographie liquide (CLHP) ou en phase gazeuse couplée à la spectrométrie de masse (CG-SM), ainsi que la spectroscopie ultraviolet-visible ou infrarouge à transformée de Fourier (FTIR). La DSC est la technique de choix pour établir le critère de pureté et la FTIR la plus rapide. La CG-SM est nécessaire à l’identification des impuretés volatiles, tandis que la CLHP permet de détecter les fullerènes lourds et les dérivés du C₆₀. La deuxième partie a porté sur des aspects fonctionnels des fullerènes et nous avons, pour cela, utilisé des préparations pures selon les critères définis précédemment. Dans un premier temps, nous avons cherché à préciser le sous-compartiment cellulaire ciblé par le C₆₀ injecté in vivo chez la souris. Après administration d’une solution huileuse, les molécules de C₆₀ sont retrouvées dans le foie et la rate, à l’intérieur des cellules, parfois au niveau des mitochondries et du réticulum endoplasmique. La présence des molécules de C₆₀, au niveau des mitochondries a été corroborée par la mise en évidence de modifications spécifiques d’activité des enzymes de la mitochondrie (malate déshydrogénase et complexe I de la chaîne respiratoire). Dans un deuxième temps, nous avons abordé l’effet des fullerènes sur des cellules intervenant dans une dysrégulation immunologique où l’inflammation joue un rôle important : l’allergie. L’évènement cellulaire à l’origine des symptômes allergiques est la libération de médiateurs de l’inflammation et de la réponse immunitaire lors de l’activation dépendante des IgE des basophiles et des mastocytes. L’effet régulateur de C₆₀ et de quatre dérivés hydrosolubles, le fullérol, la β-cyclodextrine C₆₀, le dendro C₆₀ et le C₆₀ serinol-malonate, a été testé. L’innocuité des dérivés à des concentrations nanomolaires et leur pouvoir inhibiteur sur la dégranulation IgE et non IgE dépendante des lignées mastocytaires de rat a été vérifié in vitro. Dans un test d’activation cellulaire mesurant l’expression des marqueurs CD63 et CD203c par cytométrie de flux, nous montrons que les différents dérivés sont capables d’interférer ex vivo avec l’activation de basophiles de patients allergiques dans des conditions naturelles de sang total. Les taux d’inhibition dépendent des dérivés et des patients avec un maximum observé à 35% en présence de C₆₀ serinol-malonate. Ces inhibitions ont été reproduites sur des basophiles humains purifiés en étudiant des marqueurs d’activation supplémentaires CD107a et CD69. Les perspectives de ce travail portent sur la spécificité et les mécanismes d’inhibitions observés au niveau intracellulaire. Elles incluent, par exemple, l’étude des flux de calcium ou des protéines de fusion, ou des facteurs de transcription.
Article
Such carbon structures as fullerenes, endofullerenes, nanotubes, nanodiamonds, and graphenes, which were discovered over recent decades, possess a number of unique properties and can become the basis for the design of a new class of neuroprotective agents; however, despite years of research, this has not happened yet. In the first part of the review, the significance of the functionalization of carbon nanoparticles for their use in biology and medicine is described, and the data on their toxicity are also discussed. The second part presents the works of Russian and foreign scientists demonstrating the neuroprotective properties of carbon nanoparticles and the possibilities of their application in neurobiology and neurology. The successful experience of such experiments is described and the existing problems are indicated.
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В работе изучалась возможность использования водорастворимого фуллерена в производстве хлеба. Фуллерены – это аллотропнная модификация углерода. Они биологически активны и используется в медицине, в качестве антиоксидантов, радиопротекторов, противогрибковых и других агентов. Поэтому возник интерес по изучению влияния водорастворимого фуллерена на хлебопекарные дрожжи и процесс брожения при производстве хлеба. Основными факторами, влияющими на технологический процесс и качество готовых хлебобулочных изделий, является биологическая активность дрожжей и молочнокислых бактерий. В работе в качестве контрольного образца выбрана рецептура хлеба пшеничного из муки высшего сорта. Фуллерен растворялся в воде и вносился в виде водного раствора при замесе теста. Замес проводили вручную на дрожжах фирмы Angel, способ приготовления хлеба выбран ускоренный. Перед замесом теста проводили активацию дрожжей в воде (контроль) и в растворах фулеррена (1; 1,5; 2; 3; 4 и 4,5 %) с добавлением 10 % муки от ее количества, идущего на замес. Активацию проводили в течение 20 и 60 минут и наблюдали за образованием «пенной шапочки». В результате в образцах с добавлением водорастворимого фуллерена с увеличением количества добавки наблюдалось увеличение объема «пенной шапочки», что говорит об активизации деятельности дрожжей и ускорении процесса брожения. Готовые образцы изделий исследовали по основным показателям качества. Результаты показали, что с добавлением водорастворимого фуллерена изменялась окраска изделий, незначительно увеличивалась кислотность при прочих равных условиях, что тоже говорит о более быстром кислотонакоплении, что влияет на процесс созревания теста и продолжительность брожения. Пористость готового хлеба также увеличивалась с увеличением дозировки фуллерена. В результате проведенных исследований по влиянию водорастворимого фуллерена на хлебопекарные свойства дрожжей установлено его положительное влияние на процесс брожения и качество хлеба.
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Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia. And, oxidation/antioxidant imbalance plays an important role in the progress of IPF. Fullerene is considered to be a novel "structural" antioxidant. This study aimed to explore if water-soluble C60 (C60(OH)22) can exhibit antifibrotic activity in its antioxidant role. Methods: Healthy C57BL/6J mice were randomly grouped and induced pulmonary fibrosis by intratracheal injection of bleomycin. Results: The survival rate of mice was observed and found that 10mg/kg was the optimal dose of water-soluble C60 for pulmonary fibrosis. We observed that water-soluble C60 can alleviate the severity of pulmonary fibrosis by observing the chest computed tomography, pulmonary pathology, and content of collagen, alpha smooth muscle actin and fibronectin in lung. Compared with bleomycin group, ROS, the content of TNF-α in BALF, and the number of fibroblasts was significantly decreased and the number of type Ⅱ alveolar epithelial cells was increased after treatment with C60. Conclusion: Therefore, thanks to its powerful antioxidant action, water-soluble C60 can reduce the severity of pulmonary fibrosis induced by bleomycin in mice.
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Aims The aim of the study was to determine the protective and therapeutic effect of fullerene C60 nanoparticle on DMBA-induced breast cancer in rats. Main methods In vitro cell viability was determined by the WST-1 test. In vivo analysis was performed in female Wistar Albino rats. The expression of caspase-3, Bcl-2, Nrf-2, NF-κB, TNF-α, COX-2, p53, IL-6, IL-1α ve p38α (MAPK) proteins were assessed by western blotting. Furthermore, malondialdehyde (MDA), glutathione (GSH), catalase activity (CAT), total protein levels and DNA damage were investigated. In addition, tissues were evaluated by histopathologically. In in silico analysis, the binding affinities of the fullerene C60 nanoparticle to transcription factors such as caspase-3, Bcl-2, Nrf-2, NF-κB, TNF-α, COX-2, VEGF and Akt were demonstrated by molecular docking. Key findings Treatment of MCF-7 cells at various concentrations of fullerene C60 (0.1 to 100 mg/ml) inhibited cell viability in a dose dependent manner. Fullerene C60 treated rats exhibited considerable increase in the level of caspase-3 while decrease in the level of pro-survival protein Bcl-2. Bcl-2, NF-κB, TNF-α, COX-2, IL-6, IL-1α and p38α (MAPK) protein expression levels and malondialdehyde (MDA) levels were decreased in the C60 + DMBA groups compared to the DMBA group. It was observed that caspase-3, Nrf-2 and p53 protein expression levels, glutathione (GSH) level, catalase activities (CAT) and total protein levels increased significantly which was further confirmed through the resulting DNA fragmentation. Significance In silico assays, fullerene C60 has been observed to have similar affinity to some crystal ligands, especially against cancer.
Nowadays, with the increasing proportion of the aging population, more and more elderly people suffer from aging-related diseases. Evidences said that aging may be the result of genetic regulation. Even if aging is inevitable, prolonging the time of healthy aging, delaying the progression of aging-related diseases and the incidence of morbidity can greatly alleviate the pressure on individuals and society. Today, the research and exploration of aging in the field of materials is increasing. Here, we have a rough summary of recent researches of aging in the field of nanomaterials. Some nanomaterials such as silica NMs and carbon nanotubes can cause damage to the cells, which may due to aging. Other nanomaterials such as Fullerenes and metal based nanomaterials with reducing properties can protect the body from endogenous and exogenous harmful substances such as ROS to some extent by virtue of their excellent reducing properties. Another new type of nucleic acid nanomaterial, Tetrahedral framework nucleic acids, is not limited to avoiding cell damage. It selectively clearance existing senescent cells in the tissue, and this effect also avoids the chronic inflammatory environment caused by senescent cells secreting senescence-associated secretory phenotype to the surroundings. We believe that the potential in the field of nanomaterials is enormous, and today's research results are just the tip of the iceberg. There are still a lot of space of nanomaterials to explore in the aging field.
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The present study delineates the effects of incorporation of 1% diallyl sulfide (DAS) into extra virgin olive oil (EVOO) on the physico‐chemical characteristics, in vitro antioxidant, and in vivo hepatoprotective properties in CCl4‐induced acute liver injury in mice. Results showed that the DAS‐rich EVOO exhibited good oxidative stability over one‐month storage and preserved its original quality‐related parameters including major components (oleic acid, linoleic acid, and palmitic acid), and minor components (tocopherols, chlorophylls and carotenoids, tyrosol, hydroxytyrosol, elenolic acid, oleuropein and its aglycone, pinoresinol, vanilic acid, cinnamic acid, ferulic acid, luteolin, apigenin, and sterols). Compared with EVOO or DAS, the DAS‐rich EVOO displayed the highest DPPH and ABTS‐radical scavenging activities and showed the strongest cellular antioxidant activity (CAA). In connection with its free radical scavenging activity and CAA, DAS‐rich EVOO significantly normalized the serum ALT and AST levels and prevented the increase in interleukin‐6 in CCl4‐intoxicated mice. The manifest anti‐inflammatory and hepatoprotective effects of DAS‐rich EVOO were further supported by liver histopathological examinations. Overall, the EVOO enrichment with DAS could open up opportunities for the development of novel functional food with improved antioxidant and hepatoprotective properties. The enrichment of extra virgin olive oil (EVOO) with diallyl sulfide (DAS) improves its anti‐radical, ferric reducing power, and cellular antioxidant activities. It also underpins its anti‐inflammatory and protective effect on CCl4‐intoxicated mice. The EVOO enrichment with DAS could open up opportunities for the development of novel functional food.
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Nutrition (diet composition and eating regimen) is one of the key factors of longevity. A balanced diet allows you to avoid essential nutrient deficiencies and hazardous substances to metabolic health. A healthy diet, containing enough dietary fibers, polyphenols, and metabiotics, maintains an optimal quantitative and qualitative balance of the microbiota. Aging is a complex of chronic inflammation and stress processes, so anti-inflammatory nutrients, antimutagens, and hormetins are an integral part of a longevity diet. One of the factors of inflammation is a hyperglycemic diet. Controlling the levels of simple carbohydrates (glucose, fructose, galactose) in the diet can reduce the level of glycation in tissues, which is a fundamental mechanism of aging. Several biologically active substances in food are capable of targeted suppression of aging-associated signaling pathways and activating pro-longevity stress-resistance. Diet personalization is the future of preventive medicine, taking into account markers of metabolic health, the nutritional density of the diet, and markers of biological age.
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Technologies that manipulate matter on the nanoscale have the potential to virtually affect every part of our daily lives. Products resulting from use of these technologies may result in oral exposure of consumers to nanosized materials when used as intended, resulting in contact with the gastrointestinal tract (GIT). Maintenance of a healthy GIT is essential for limiting systemic exposure to ingested substances, and any substance that compromises the structure or function of this barrier may be expected to display significant systemic toxicity also. Therefore, toxicity to the GIT is an important consideration when assessing the effects of oral exposure to nanomaterials. This chapter will summarize the available evidence from in vitro and in vivo studies concerning the direct effects of nanomaterials on the structure and barrier function of the GIT, focusing on nanosized materials for which oral exposure is most prevalent for average consumers: titanium dioxide, silica, nanosilver, and zinc oxide nanoparticles.
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Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a ubiquitous multifunctional protein required in the DNA base excision repair pathway and a noteworthy reducing-oxidizing factor that regulates the activity of various transcription factors. Cyclin-dependent kinases (CDKs) assume a key role in directing the progression of the cell- cycle. The present study evaluated the synergistic efficacy of using licochalcone B (LCB) and fullerene C60 (FnC60) nanoparticles against diethylnitrosamine (DEN)-induced hepatocarcinoma in rats and relevant signaling pathways, with APE1/Ref-1 and CDK-4, as novel anti-cancer- targeting. LCB alone and in combination with FnC60 significantly decreased DNA fragmentation, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine levels), APE1/Ref-1, CDK-4, retinoblastoma, B- cell lymphoma-2 (Bcl-2), B-cell lymphoma-xL (Bcl-xL), and β-arrestin-2 mRNA expression, and APE1/Ref-1 and CDK-4 protein expression. In contrast, these treatments significantly increased the expression of protein 53 (p53), Bcl-2-associated X protein (Bax), and caspase-3. These data suggest that LCB either alone or in combination with FnC60 elicited significant protective effects against DEN-induced hepatocarcinogenesis, which may have occurred because of the regulation of enzymes involved in DNA repair and cell-cycle control at S phase progression as well as the induction of apoptosis at the gene and protein expression levels. Furthermore, FnC60 potentiated the effect of LCB at the molecular level, possibly through targeting of cancerous cells.
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Lipid droplets (LDs) were considered as a mere lipid storage organelle for a long time. Recent evidence suggests that LDs are in fact distinct and dynamic organelles with a specialized proteome and functions in many cellular roles. As such, LDs contribute to cellular signaling, protein and lipid homeostasis, metabolic diseases and inflammation. In line with the multitude of functions, LDs interact with many cellular organelles including mitochondria, peroxisomes, lysosomes, the endoplasmic reticulum and the nucleus. LDs are highly mobile and dynamic organelles and impaired motility disrupts the interaction with other organelles. The reduction of interorganelle contacts results in a multitude of pathophysiologies and frequently in neurodegenerative diseases. Contacts not only supply lipids for β-oxidation in mitochondria and peroxisomes, but also may include the transfer of toxic lipids as well as misfolded and harmful proteins to LDs. Furthermore, LDs assist in the removal of protein aggregates when severe proteotoxic stress overwhelms the proteasomal system. During imbalance of cellular lipid homeostasis, LDs also support cellular detoxification. Fine-tuning of LD function is of crucial importance and many diseases are associated with dysfunctional LDs. We summarize the current understanding of LDs and their interactions with organelles, providing a storage site for harmful proteins and lipids during cellular stress, aging inflammation and various disease states.
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An in vivo biotransformation of [60] fullerene is observed that does not follow a usual redox metabolic pathway. Following the administration of a single dose of micronized C-60 to Swiss mice, C-60-retinol and retinyl palmitate adducts were identified in liver by UV/VIS spectroscopy and mass spectrometry after high performance liquid chromatography. NMR investigations of the main biotransformed compound, after in vitro synthesis, show cycloaddition of retinol to C-60. The observed biotransformation, which proves that C-60 does not remain unchanged in the liver as believed previously, also shows that Diels-Alder-like reactions can occur in vivo.
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High amounts of micronized C-60 have been injected intraperitoneally into Swiss mice. Until the fourteenth day, they were still alive without any behaviour trouble. C-60 was well absorbed, and found localized in spleen and liver. Inside the liver, C-60 was detected in Kupffer cells and hepatocytes. But the main result is the induced hypertrophy of the perisinusoidal cells, where C-60 preferentially accumulates.
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Olive oil is suggested a new solvent for C60 which offers the possibility to deliver in a biocompatible from this compound to biosystems and living organisms. This allows investigating for the first time the true biocompatibility and toxicity of C60.
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It has been revealed for the first time that sodium fullerenolate Na(4)[C(60)(OH)(∼30)] (NaFL), a water soluble polyhydroxylated [60]fullerene derivative, destroys amyloid fibrils of the Aβ(1-42) peptide in the brain and prevents their formation in in vitro experiments. The cytotoxicity of NaFL was found to be negligibly low with respect to nine different culture cell lines. At the same time, NaFL showed a very low acute toxicity in vivo. The maximal tolerable dose (MTD) and LD50 for NaFL correspond to 1000 mg kg(-1) and 1800 mg kg(-1), respectively, as revealed by in vivo tests in mice using intraperitoneal drug injection. The observed pronounced anti-amyloid activity and low toxicity of NaFL make it a very promising lead drug for the development of potent fullerene-based therapeutic approaches for the treatment of amyloidoses, such as Alzheimer's disease and others.
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Recent toxicology studies suggest that nanosized aggregates of fullerene molecules can enter cells and alter their functions, and also cross the blood-brain barrier. However, the mechanisms by which fullerenes penetrate and disrupt cell membranes are still poorly understood. Here we use computer simulations to explore the translocation of fullerene clusters through a model lipid membrane and the effect of high fullerene concentrations on membrane properties. The fullerene molecules rapidly aggregate in water but disaggregate after entering the membrane interior. The permeation of a solid-like fullerene aggregate into the lipid bilayer is thermodynamically favoured and occurs on the microsecond timescale. High concentrations of fullerene induce changes in the structural and elastic properties of the lipid bilayer, but these are not large enough to mechanically damage the membrane. Our results suggest that mechanical damage is an unlikely mechanism for membrane disruption and fullerene toxicity.
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Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols), have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF) and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF). We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF.
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Studies reporting on potentially toxic interactions between aqueous fullerene nanoparticles (nC(60)) and microorganisms have been contradictory. When known confounding factors were avoided, growth yields of Saccharomyces cerevisiae and Escherichia coli cultured in the presence and absence of independently prepared lots of underivatized nC(60) were found not to be significantly different.
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In this study, the ability of the C(60) fullerene derivative DF-1 to protect radiosensitive cells from the effects of high doses of gamma irradiation was examined. Earlier reports of DF-1's lack of toxicity in these cells were confirmed, and DF-1 was also observed to protect both human lymphocytes and rat intestinal crypt cells against radiation-induced cell death. We determined that DF-1 protected both cell types against radiation-induced DNA damage, as measured by inhibition of micronucleus formation. DF-1 also reduced the levels of reactive oxygen species in the crypt cells, a unique capability of fullerenes because of their enhanced reactivity toward electron-rich species. The ability of DF-1 to protect against the cytotoxic effects of radiation was comparable to that of amifostine, another ROS-scavenging radioprotector. Interestingly, localization of fluorescently labeled DF-1 in fibroblast was observed throughout the cell. Taken together, these results suggest that DF-1 provides powerful protection against several deleterious cellular consequences of irradiation in mammalian systems including oxidative stress, DNA damage, and cell death.
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Application of nanotechnology to medical biology has brought remarkable success. Water-soluble fullerenes are molecules with great potential for biological use because they can endow unique characteristics of amphipathic property and form a self-assembled structure by chemical modification. Effective gene delivery in vitro with tetra(piperazino)fullerene epoxide (TPFE) and its superiority to Lipofectin have been described in a previous report. For this study, we evaluated the efficacy of in vivo gene delivery by TPFE. Delivery of enhanced green fluorescent protein gene (EGFP) by TPFE on pregnant female ICR mice showed distinct organ selectivity compared with Lipofectin; moreover, higher gene expression by TPFE was found in liver and spleen, but not in the lung. No acute toxicity of TPFE was found for the liver and kidney, although Lipofectin significantly increased liver enzymes and blood urea nitrogen. In fetal tissues, neither TPFE nor Lipofectin induced EGFP gene expression. Delivery of insulin 2 gene to female C57/BL6 mice increased plasma insulin levels and reduced blood glucose concentrations, indicating the potential of TPFE-based gene delivery for clinical application. In conclusion, this study demonstrated effective gene delivery in vivo for the first time using a water-soluble fullerene.
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The results of a laser flash photolysis investigation of a dendritic methano[60]fullerene octadeca-acid (DA) and its tert-butyl ester (DE) are reported. DE possesses photophysical properties typical of a [60]fullerene mono-adduct with a singlet oxygen quantum yield approaching unity in toluene and a triplet absorption spectrum with a maximum at 710 nm. In methanol DA also possesses properties typical of a [60]fullerene mono-adduct, but in aqueous solution its photophysical behaviour shows a degree of aggregation that is a function of pH and concentration. At pH 7.4 and higher, Coulombic repulsion between de-protonated carboxylate groups reduces the propensity to aggregation and dilute solutions (<10−4 M) of DA exhibit typical [60]fullerene mono-adduct behaviour, although the singlet oxygen yield of 0.75 is lower than in methanol (0.93). The rate constant for DA triplet state quenching by oxygen in water (pH 7.4) is relatively low, which reflects shielding of the hydrophobic C60 core by the dendrimer thus reducing the possibility of orbital overlap with oxygen due to restricted diffusion. Aggregation is evident from the UV-VIS absorption spectra at concentrations exceeding 10−4 M in water at pH 7.4, beyond which substantial positive deviations from the Beer–Lambert law are observed. In acidic solutions (pH 4.5) the degree of dissociation of the carboxylic acid groups is negligible and the lack of Coulombic repulsion between DA molecules leads to extensive aggregation, even in dilute solutions. In such solutions the singlet oxygen quantum yield is greatly reduced (0.13 at pH 4.5).
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Aqueous solutions of highly stable supramolecular donor-acceptor complexes of chemically nonmodified pristine C(60) fullerene molecules with H(2)O molecules (hydrated C(60) fullerene-C(60)HyFn) and their labile nano-sized clusters were examined for their antioxidant effects on removal of hydroxyl radicals (.OH) and protecting DNA against oxidative damage induced by ionizing radiation in vitro. The suppressing influence of C(60)HyFn on the formation of OH-radicals in water exposed to X-rays at doses of 1-7 Gy was assessed by determination of oxidation levels of coumarin-3-carboxylic acid. C(60)HyFn demonstrates apparent antiradical activity in vitro in the range of concentrations of 10(-11)-10(-6) M. Paradoxically, the .OH-removing efficacy of C(60)HyFn was in reverse correlation with fullerene concentration. It was hypothesized that the antiradical action of C(60)HyFn in water medium generally is due to a "nonstoichiometric" mechanism, supposedly to a hydrated free radical recombination (self-neutralization), which is catalyzed by specific water structures ordered by C(60)HyFn. With the use of 8-oxoguanine as a marker of oxidative damage to DNA, it has been demonstrated that C(60)HyFn in concentrations of 10(-7)-10(-6) M protects nucleic acids against radical-induced damage. The second part of the present study was aimed to evaluate the overall radioprotective efficacy of C(60)HyFn in doses of 0.1 or 1 mg/kg b.w. injected intraperitoneally to mice either 1 h before or 15 min after lethal dose exposure of the X-ray (7 Gy) irradiation. Survival rate of the mice was observed at 30 day intervals after irradiation, while the weight gains of experimental animals were monitored as well. The most significant protective effect was demonstrated when 1 mg/kg dosage of C(60)HyFn was administered before irradiation. The outcome of the substance testing is 15% survival rate of irradiated animals at 30 days of observation, and prevention of noticeable weight loss characteristic for radiation impact, versus unprotected control animals. In conclusion, results of the study obviate that the apparent protective action of C(60)HyFn in vivo is determined by its considerable ability to decrease X-ray-generated reactive oxygen species. Based on the results and that neat C(60) is nontoxic, actually in the hydrated form, without side effects and with sufficient radioprotective effects in low doses, C(60)HyFn may be considered as a novel antioxidant agent, which substantially diminishes the harmful effects of ionizing radiation.
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C60 fullerenes and single-walled carbon nanotubes (SWCNT) are projected to be used in medicine and consumer products with potential human exposure. The hazardous effects of these particles are expected to involve oxidative stress with generation of oxidatively damaged DNA that might be the initiating event in the development of cancer. In this study we investigated the effect of a single oral administration of C60 fullerenes and SWCNT. We measured the level of oxidative damage to DNA as the premutagenic 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in the colon mucosa, liver, and lung of rats after intragastric administration of pristine C60 fullerenes or SWCNT (0.064 or 0.64 mg/kg body weight) suspended in saline solution or corn oil. We investigated the regulation of DNA repair systems toward 8-oxodG in liver and lung tissue. Both doses of SWCNT increased the levels of 8-oxodG in liver and lung. Administration of C60 fullerenes increased the hepatic level of 8-oxodG, whereas only the high dose generated 8-oxodG in the lung. We detected no effects on 8-oxodG in colon mucosa. Suspension of particles in saline solution or corn oil yielded a similar extent of genotoxicity, whereas corn oil per se generated more genotoxicity than the particles. Although there was increased mRNA expression of 8-oxoguanine DNA glycosylase in the liver of C60 fullerene-treated rats, we found no significant increase in repair activity. Oral exposure to low doses of C60 fullerenes and SWCNT is associated with elevated levels of 8-oxodG in the liver and lung, which is likely to be caused by a direct genotoxic ability rather than an inhibition of the DNA repair system.
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A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
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The reaction of organic radicals (R[sup [sm bullet]] = benzyl, tert-butyl, trichloromethyl) with C[sub 60] and C[sub 70] has been investigated using laser flash photolysis and pulse radiolysis techniques. The alkyl radicals are very reactive toward fullerenes and form radical adducts, (RC[sub 60])[sup [sm bullet]] and (RC[sub 70])[sup [sm bullet]]. The difference absorption spectrum of (RC[sub 60][sup [sm bullet]]) exhibits broad absorption in the visible, while that of (RC[sub 70])[sup [sm bullet]] exhibits bleaching of absorption in the region 440-560 nm. The rate constants for the reaction of these radicals with fullerenes are in the range of 10[sup 8] M[sup [minus]1] s[sup [minus]1] for dichloromethyl to diffusion controlled for tert-butyl radicals. 30 refs., 6 figs., 1 tab.
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The fate of oily vehicles administered intramuscularly was followed with whole body gamma-scintigraphy. Groups of six rabbits received injections administered into the upper hind leg. No differences were observed in disappearance rates of various volumes (50–400 μl) of either fractionated coconut oil or sesame oil. Addition of two different concentrations of a drug substance, zuclopenthixol decanoate, to fractionated coconut oil did not influence the disappearance rate of the vehicle. Half-lives of the two oils at the injection site were in the order of 1 week for fractionated coconut oil and 1 month for sesame oil. Both oils spread approximately 25% along the muscle fibres during the first 24 h after administration. Radioactivity was mainly excreted with the urine. Insignificant amounts of radioactivity were found in blood, liver and carcass after 10 days.
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The influence of fullerene soot as well as pure C60 on the oxidation stability of rapeseed oil is studied. Fullerene soot (C60 content between 0–6 wt.%) was synthesized by using a carbon arc method. Differential scanning calorimetry was applied to estimate the oxidation induction time of fullerene‐oil composites. The addition of fullerene soot significantly hampered the peroxide formation thus increasing of oxidation stability of tested oils.
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A series of fatty acid esters of glycerol as linseed, sunflower, soybean and olive oils have been tested as C60 fullerene solvents together with a mixture of methyl ester fatty acids derived from brassica oilseeds and used as a biofuel known as “biodiesel.” All the oils evaluated are effective solvents of C60. The solubility of C60 in the selected vegetable oils has been determined spectrophotometrically. The C60 solubility in vegetable oils may pave the way for easier application of C60 fullerene in medicinal chemistry and in additive chemistry for varnishes and fuels. It has been found that C60 is not only soluble in the fatty acid esters but is also reactive with them under mild conditions, giving addition products easily recognized by a characteristic absorption band at 435 nm. The addition reaction mechanism has been discussed.
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The autoxidation of pyrogallol was investigated in the presence of EDTA in the pH range 7.9–10.6. The rate of autoxidation increases with increasing pH. At pH 7.9 the reaction is inhibited to 99% by superoxide dismutase, indicating an almost total dependence on the participation of the superoxide anion radical, O2·−, in the reaction. Up to pH 9.1 the reaction is still inhibited to over 90% by superoxide dismutase, but at higher alkalinity, O2·− -independent mechanisms rapidly become dominant. Catalase has no effect on the autoxidation but decreases the oxygen consumption by half, showing that H2O2 is the stable product of oxygen and that H2O2 is not involved in the autoxidation mechanism. A simple and rapid method for the assay of superoxide dismutase is described, based on the ability of the enzyme to inhibit the autoxidation of pyrogallol. A plausible explanation is given for the non-competitive part of the inhibition of catechol O-methyltransferase brought about by pyrogallol.
Article
As unique nanoparticles, fullerenes have attracted much attention due to their unparalleled physical, chemical and biological properties. Various functionalized fullerenes with -OH, -NH2, -COOH, and peptide modifications were developed. It summarized the biological activities of fullerenes derivatives in cancer therapy with high efficiency and low toxicity, as reactive oxygen species scavenger and lipid peroxidation inhibitor, to inhibit human immunodeficiency virus and to suppress bacteria and microbial at low concentration. In addition, the mechanism for fullerene to enter cells and biodistribution of fullerene in vivo was also discussed. This research focuses on the current understanding of fullerenes-based nanomaterials in the potential clinical application as well as biological mechanism of fullerenes and its derivatives in disease therapy. Keywordsfullerene-nanoparticle-nanomedicine-clinical application-biological effect
Article
This work is an evaluation of the quality of three introduced European olive cultivars Arbequina, Coratina, and Koroneiki grown under a biological agricultural system in the arid zone of Sfax in Tunisia compared to Chemlali cultivars. Various olive parameters were analyzed, such as ripening index, pulp/stone (P/S) ratio and oil content. We have considered the regulated physicochemical analytical parameters, fatty acids and minor compounds for olive oil. The most of the quality indices and fatty acid composition showed significant variations among olive cultivars. The Koroneiki, Coratina and Chemlali Zarzis cultivars had highest values of oleic acid (62.7%) (76.8%, 75.8% and 73.9%, respectively), Arbequina, had lowest value of oleic acid and similar to Chemlali Sfax. Coratina was noteworthy for its higher content of phenolic compounds (287.8 mg kg−1), oil content (42.4%) and P/S ratio (4.7%). Although their low phenol contents, autochthonous cultivars presented high contents of α-tocopherol (577.8 and 434.6 mg kg−1 for Chemlali Boughrara and Chemlali Zarzis, respectively) except for Chemlali Sfax. In conclusion, European cultivars seem to have adapted to the area studied according to their oil biochemical composition while the increase observed in their α-tocopherol levels. The cultivar Arbequina showed a similar composition of Chemlali Sfax.
Article
Immunomodulating peptide tuftsin (Thr-Lys-Pro-Arg) was covalently conjugated to fullerene C(60) by two different ways to prepare NH(2)-tuftsin-C(60) and C(60)-tuftsin-COOH. The two new compounds were intensively characterized. The synthetic C(60)-tuftsin conjugates were assayed for their stability against leucine aminopeptidase degradation. And the immunostimulating activities to murine peritoneal macrophages were investigated in vitro. Compared with the natural tuftsin, significant enhancement of phagocytosis, chemotaxis activities and major histocompatibility complex class II (MHC II) molecule expression were observed in macrophages stimulated by both of the conjugates. The two conjugates also exhibit complete resistance to enzymatic hydrolysis, and they are non-toxic to macrophages in the tested concentrations. On all accounts, these results suggest that the C(60)-tuftsin conjugates can be used as potential candidates of immunomodulators and vaccine adjuvants.
Article
We examined the biodistribution of C(60) in rats after tail vein administration using LC-MS/MS. C(60) was detected in various tissues, such as brain, kidneys, liver, lungs, and spleen of rats. On the other hand, no C(60) was found in blood. The highest C(60) concentration was observed in the lungs, followed by spleen, liver, kidneys, and brain. These results suggested that C(60) injected in the tail vein could be filtered by lung capillary vessels and accumulate in the lungs prior to being distributed to other tissues. Moreover, C(60) not being detected in the blood indicates that clearance of C(60) from the blood by filtration might effectively occur in the lungs. The time-dependent variation in the biodistribution of C(60) was evaluated. A time-dependent decrease in C(60) concentrations was observed in all tissues, except spleen. Moreover, a decreasing trend of C(60) levels differed among tissues, which could be due to differences in accumulation. These results suggest that unmodified C(60) and/or C(60) metabolites by metabolic enzymes could be excreted into feces and/or urine. In further studies, the metabolic and excretion pathways of C(60) should be evaluated to understand the toxicokinetics of C(60).
Article
This review aims to clarify inconsistencies in previous reports regarding the potential for aqueous aggregates of fullerenes (nC60) to generate reactive oxygen species (ROS) and cause toxicity in fish. Methods for evaluation of ROS production and toxicity of aqueous nC60 have evolved over time and limitations in initial studies have led to unintentional erroneous reports of nC60 ROS generation and toxicity. Some of these reports continue to lead to misconceptions of the environmental effects of C60. Critical review of the evidence (2007-2011) indicates that aqueous nC60 have minimal potential to produce ROS and that oxidative stress in fish is not induced by environmentally relevant exposure to nC60. Future studies should acknowledge that current evidence indicates low toxicity of nC60 and refrain from citing articles that attribute toxicity in fish to nC60 based on methods shown to be compromised by experimental artifacts. Despite low toxicity of nC60 in fish, an emerging environmental issue is that nC60 can affect environmental fate, transport, and bioavailability of co-contaminants in aquatic environments in a similar manner to that observed for other anthropogenic particulates (e.g., microplastics).
Article
Fullerene (carbon sixty [C60]) has potential industrial and medical applications. In the future, people working in or residing near manufacturing facilities may be exposed to C60. Therefore, quantitative data on long-term C60 clearance from the lungs are required. To estimate the clearance rate and deposition fraction of C60 from inhalation exposure, the C60 burden in the lungs, liver, and brain of rats was determined after intratracheal instillation and inhalation. Male Wistar rats were intratracheally instilled with different concentrations of a C60 suspension prepared with Tween 80 (geometric mean [GM] of particle diameter based on number, 18–29 nm; geometric standard deviation [GSD] of particle diameter, 1.5; and doses, 100, 200, and 1000 micrograms per body) or exposed to a C60 aerosol prepared with nebulizer (GM of particle diameter based on number, 96 nm; GSD of particle diameter, 2.0; and exposure level, 120 μg/m3). C60 burden in the lungs, liver, and brain was determined at various time points (1 h to 6 months) by a newly developed sensitive high-performance liquid chromatography-ultraviolet absorptiometry combined with extraction and concentration of C60 from the organs. C60 clearance was evaluated using a 2-compartment model: fast clearance after deposition on lung surface and slow clearance after retention in the epithelium. The detection limit of our analysis method was 8.9 ng/g tissue. Pulmonary C60 burden decreased with time and depended on the C60 concentration administered. The concentration of C60 in the liver and brain was below the detection limit: 8.9 ng/g tissue. The half-life of intratracheally instilled C60 was 15–28 days. The deposition mass fraction of inhaled C60 was 0.14. Mode evaluation revealed that most instilled particles could be eliminated by the fast clearance pathway. This finding is consistent with the transmission electron microscopy finding that many particles were present in alveolar macrophages.
Article
Colloidal fullerene nanoparticles (nC60) were reported to be toxic to fish brains, human cells and microorganisms, while new observations suggest that the observed toxicity may be due to tetrahydrofuran (THF) solvent or its oxidative by-products in nC60 preparations. Here, we report a novel method for preparing nC60 nanoparticles that does not use THF solvent, but provides nC60 with an average particle size of 43.8 nm and a yield approximately 100 times higher than the THF method. The prepared nC60 showed a similar antioxidant capacity compared to a water-soluble vitamin E analog. No mortality to human epidermal keratinocytes was observed at a concentration 170 times higher than the reported LC50 values for other human cell lines. No toxicity was observed to E. coli or B. subtilis at up to 342 microg/mL nC60 for 16 h, which was hundred times higher than the reported minimum inhibitory concentrations of nC60 prepared using THF method for these two bacteria. When E. coli was exposed to 85.5 microg/mL nC60 with daily passage for 4 days, the stationary phase populations at different passages were not statistically different (p = 0.05) from the control without nC60 nanoparticles. These results reveal that the intrinsic biological property of nC60 is non-toxic, confirming the prior non-toxic reports when using nC60 prepared with non-THF methods.