Versatile applications of fullerenol nanoparticles.

Nanomaterials have become increasingly important over time as research technology has enabled the progressively precise study of materials at the nanoscale. Developing an understanding of how nanomaterials are produced and tuned allows scientists to utilise their unique properties for a variety of applications, many of which are already incorporated into commercial products. Fullerenol nanoparticles C60(OH)n, 2 ≤ n ≤ 44 are fullerene derivatives and are produced synthetically. They have good biocompatibility, low toxicity and no immunological reactivity. In addition, their nanometre size, large surface area to volume ratio, ability to penetrate cell membranes, adaptable surface that can be easily modified with different functional groups, drug release, high physical stability in biological media, ability to remove free radicals, magnetic and optical properties make them desirable candidates for various applications. This review comprehensively summarises the various applications of fullerenol nanoparticles in different scientific fields such as nanobiomedicine, including antibacterial and antiviral agents, and provides an overview of their use in agriculture and biosensor technology. Recommendations are also made for future research that would further elucidate the mechanisms of fullerenols actions.

The Puzzling Potential of Carbon Nanomaterials: General Properties, Application, and Toxicity.

Being a member of the nanofamily, carbon nanomaterials exhibit specific properties that mostly arise from their small size. They have proved to be very promising for application in the technical and biomedical field. A wide spectrum of use implies the inevitable presence of carbon nanomaterials in the environment, thus potentially endangering their whole nature. Although scientists worldwide have conducted research investigating the impact of these materials, it is evident that there are still significant gaps concerning the knowledge of their mechanisms, as well as the prolonged and chronic exposure and effects. This manuscript summarizes the most prominent representatives of carbon nanomaterial groups, giving a brief review of their general physico-chemical properties, the most common use, and toxicity profiles. Toxicity was presented through genotoxicity and the activation of the cell signaling pathways, both including in vitro and in vivo models, mechanisms, and the consequential outcomes. Moreover, the acute toxicity of fullerenol, as one of the most commonly investigated members, was briefly presented in the final part of this review. Thinking small can greatly help us improve our lives, but also obliges us to deeply and comprehensively investigate all the possible consequences that could arise from our pure-hearted scientific ambitions and work.

Hepatoprotective effect of fullerenol/doxorubicin nanocomposite in acute treatment of healthy rats.

In our recent studies we have designed fullerenol/doxorubicin nanocomposite (FNP/DOX) as the new drug nanocarrier. This research has demonstrated that this novel nanocomposite has had better implications on the liver tissue in vivo (Wistar rats treated intraperitoneally), than treatment based only on DOX. FNP/DOX has been characterised by DLS, TEM and AFM measurements which have shown that DOX loaded onto FNP did not influence fullerenol nanoparticle's size. FNP/DOX affected oxidative status in blood causing a significant decrease of catalase and SOD activity in comparison to DOX, implicating the reduction in oxidative stress. qRT-PCR results on the mRNA level of antioxidative enzymes (catalase and MnSOD) revealed that the effect of oxidative stress is significantly reduced by the treatment with FNP/DOX (p < .05). The ultrastructural analysis of the liver tissue has revealed that FNP/DOX nanocomposite generated considerably less damage in the liver tissue, than DOX applied at the same dose. Hence, our results have indicated that FNP, within FNP/DOX nanocomposite, exhibits protective effects to the liver tissue of the healthy rats.

Nanoformulations of doxorubicin: how far have we come and where do we go from here?

Nanotechnology, focused on discovery and development of new pharmaceutical products is known as nanopharmacology, and one research area this branch is engaged in are nanopharmaceuticals. The importance of being nano has been particularly emphasized in scientific areas dealing with nanomedicine and nanopharmaceuticals. Nanopharmaceuticals, their routes of administration, obstacles and solutions concerning their improved application and enhanced efficacy have been briefly yet comprehensively described. Cancer is one of the leading causes of death worldwide and evergrowing number of scientific research on the topic only confirms that the needs have not been completed yet and that there is a wide platform for improvement. This is undoubtedly true for nanoformulations of an anticancer drug doxorubicin, where various nanocarrriers were given an important role to reduce the drug toxicity, while the efficacy of the drug was supposed to be retained or preferably enhanced. Therefore, we present an interdisciplinary comprehensive overview of interdisciplinary nature on nanopharmaceuticals based on doxorubicin and its nanoformulations with valuable information concerning trends, obstacles and prospective of nanopharmaceuticals development, mode of activity of sole drug doxorubicin and its nanoformulations based on different nanocarriers, their brief descriptions of biological activity through assessing in vitro and in vivo behavior.

Synergistic mitotoxicity of chloromethanes and fullerene C60 nanoaggregates in Daphnia magna midgut epithelial cells.

Adsorption of non-polar compounds by suspended fullerene nanoaggregates (nC60) may enhance their toxicity and affect the fate, transformation, and transport of non-polar compounds in the environment. The potential of stable fullerene nanoaggregates as contaminant carriers in aqueous systems and the influence of chloromethanes (trichloromethane and dichloromethane) were studied on the midgut epithelial cells of Daphnia magna by light and electron microscopy. The size and shape of fullerene nanoaggregates were observed and measured using dynamic light scattering, transmission electron microscopy, and low vacuum scanning electron microscopy. The nC60 in suspension appeared as a bulk of aggregates of irregular shape with a surface consisting of small clumps 20-30 nm in diameter. The presence of nC60 aggregates was confirmed in midgut lumen and epithelial cells of D. magna. After in vivo acute exposure to chloromethane, light and electron microscopy revealed an extensive cytoplasmic vacuolization with disruption and loss of specific structures of D. magna midgut epithelium (mitochondria, endoplasmic reticulum, microvilli, peritrophic membrane) and increased appearance of necrotic cells. The degree of observed changes depended on the type of treatment: trichloromethane (TCM) induced the most notable changes, whereas fullerene nanoaggregates alone had no negative effects. Transmission electron microscopy also indicated increased lysosomal degradation and severe peroxidative damages of enterocyte mitochondria following combined exposure to chloromethane and fullerene nanoaggregates. In conclusion, the adsorption of chloromethane by fullerene nanoaggregates enhances their toxicity and induces peroxidative mitochondrial damage in midgut enterocytes.

Fullerenol/doxorubicin nanocomposite mitigates acute oxidative stress and modulates apoptosis in myocardial tissue.

Fullerenol (C60(OH)24) is present in aqueous solutions in the form of polyanion nanoparticles with particles' size distribution within the range from 15 to 42 nm. In this research it is assumed that these features could enable fullerenol nanoparticles (FNPs) to bind positively charged molecules like doxorubicin (DOX) and serve as drug carriers. Considering this, fullerenol/doxorubicin nanocomposite (FNP/DOX) is formed and characterized by ultra-performance liquid chromatography tandem mass spectrometry, dynamic light scattering, atomic force microscopy and transmission electron microscopy. Measurements have shown that DOX did not significantly affect particle size (23 nm). It is also assumed that FNP/DOX could reduce the acute cardiotoxic effects of DOX in vivo (Wistar rats treated i.p.). In this study, quantitative real time polymerase chain reaction results have shown that treatment with DOX alone caused significant increase in mRNA levels of catalase (p < 0.05) enzyme indicating the presence of oxidative stress. This effect is significantly reduced by the treatment with FNP/DOX (p < 0.05). Furthermore, mRNA levels of antiapoptotic enzyme (Bcl-2) are significantly increased (p < 0.05) in all treated groups, particularly where FNP/DOX was applied, suggesting cell resistance to apoptosis. Moreover, ultrastructural analysis has shown the absence of myelin figures within the mitochondria in the heart tissue with FNP/DOX treatment, indicating reduction of oxidative stress. Hence, our results have implied that FNP/DOX is generally less harmful to the heart compared to DOX.

Synthesis and Characterization of Hydroxyapatite/Fullerenol Nanocomposites.

Fullerenols are polyhydroxylated, water soluble derivatives of fullerene C60, with potential application in medicine as diagnostic agents, antioxidants or nano drug carriers. This paper describes synthesis and physical characterization of a new nanocomposite hydroxyapatite/fullerenol. Surface of the nanocomposite hydroxyapatite/fullerenol is inhomogeneous with the diameter of the particles in the range from 100 nm to 350 nm. The ζ potential of this nanocomposite is ten times lower when compared to hydroxyapatite. Surface phosphate groups of hydroxyapatite are prone to forming hydrogen bonds, when in close contact with hydroxyl groups, which could lead to formation of hydrogen bonds between hydroxyapatite and hydroxyl groups of fullerenol. The surface of hydroxyapatite particles (-2.5 mV) was modified by fullerenol particles, as confirmed by the obtained ζ potential value of the nanocomposite biomaterial hydroxyapatite/fullerenol (-25.0 mV). Keywords: Hydroxyapatite, Fullerenol, Nanocomposite, Surface Analysis.

Effects of fullerenol C60(OH)24 nanoparticles on a single-dose doxorubicin-induced cardiotoxicity in pigs: an ultrastructural study.

Cardioprotective effects of fullerenol C60(OH)24 nanoparticles (FNP) were investigated in pigs after a single treatment with doxorubicin (DOX). Semithin and ultrathin sections of myocardial tissue routinely prepared for transmission electron microscopy were analyzed. Extensive intracellular damage was confirmed in cardiomyocytes of DOX-treated animals. By means of ultrastructural analysis, a certain degree of parenchymal degeneration was confirmed even in animals treated with FNP alone, including both the oral and the intraperitoneal application of the substance. The cardioprotective effects of FNP in animals previously treated with DOX were recognized to a certain extent, but were not fully confirmed at the ultrastructural level. Nevertheless, the myocardial morphology of DOX-treated animals improved after the admission of FNP. Irregular orientation of myofibrils, myofibrillar disruption, intracellular edema, and vacuolization were reduced, but not completely eliminated. Reduction of these cellular alterations was achieved if FNP was applied orally 6 h prior to DOX treatment in a dose of 18 mg/kg. However, numerous defects, including the inner mitochondrial membrane and the plasma membrane disruption of certain cells persisted. In FNP/DOX-treated animals, the presence of multinuclear cells with mitosis-like figures resembling metaphase or anaphase were observed, indicating that DOX and FNP could have a complex influence on the cell cycle of cardiomyocytes. Based on this experiment, further careful increase in dosage may be advised to enhance FNP-induced cardioprotection. These investigations should, however, always be combined with ultrastructural analysis. The FNP/DOX interaction is an excellent model for the investigation of cardiomyocyte cell death and cell cycle mechanisms.