O. A. Kyzyma

On the Origin of C60 Fullerene Solubility in Aqueous Solution

In this work, we report that the surface hydroxylation of C60 molecules is the most likely mechanism for pristine C60 fullerenes/C60 fullerene aggregate stabilization in water, being independent of the method of C60 fullerene aqueous solution preparation.

Solvatochromism and Fullerene Cluster Formation in C60/N-methyl-2-pyrrolidone

UV-Vis spectroscopy and small-angle neutron scattering experiments are performed on the cluster solution of fullerene C60 in N-methyl-2-pyrrolidone before and after dilution of the system with pure solvent. Some changes in the UV-Vis spectra showing solvatochromism at dilution are observed, while the neutron scattering signal does not change. The effect is discussed with respect to the relation between solvatochromism and cluster formation for fullerene solutions in nitrogen-containing solvents.

C60 fullerene enhances cisplatin anticancer activity and overcomes tumor cell drug resistance

We formulated and analyzed a novel nanoformulation of the anticancer drug cisplatin (Cis) with C60 fullerene (C60+Cis complex) and showed its higher toxicity toward tumor cell lines in vitro when compared to Cis alone. The highest toxicity of the complex was observed in HL-60/adr and HL-60/vinc chemotherapy-resistant human leukemia cell sublines (resistant to Adriamycin and Vinculin, respectively). We discovered that the action of the C60+Cis complex is associated with overcoming the drug resistance of the tumor cell lines through observing an increased number of apoptotic cells in the Annexin V/PI assay. Moreover, in vivo assays with Lewis lung carcinoma (LLC) C57BL/6J male mice showed that the C60+Cis complex increases tumor growth inhibition, when compared to Cis or C60 fullerenes alone. Simultaneously, we conducted a molecular docking study and performed an Ames test. Molecular docking specifies the capability of a C60 fullerene to form van der Waals interactions with potential binding sites on P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP-1), and multidrug resistance protein 2 (MRP-2) molecules. The observed phenomenon revealed a possible mechanism to bypass tumor cell drug resistance by the C60+Cis complex. Additionally, the results of the Ames test show that the formation of such a complex diminishes the Cis mutagenic activity and may reduce the probability of secondary neoplasm formation. In conclusion, the C60+Cis complex effectively induced tumor cell death in vitro and inhibited tumor growth in vivo, overcoming drug resistance likely by the potential of the C60 fullerene to interact with P-gp, MRP-1, and MRP-2 molecules. Thus, the C60+Cis complex might be a potential novel chemotherapy modification.

Comparative Analysis of the Antineoplastic Activity of C60 Fullerene with 5-Fluorouracil and Pyrrole Derivative In Vivo

The antitumor activity of pristine C60 fullerene aqueous solution (C60FAS) compared to 5-fluorouracil (5-FU) and pyrrole derivative 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2.5-dione (MI-1) cytostatic drugs was investigated and analyzed in detail using the model of colorectal cancer induced by 1.2-dimethylhydrazine (DMH) in rats. The number, size, and location of the tumors were measured, and the pathology was examined. It was found that the number of tumors and total lesion area decreased significantly under the action of C60FAS and MI-1. Because these drugs have different mechanisms of action, their simultaneous administration can potentially increase the effectiveness and significantly reduce the side effects of antitumor therapy.

Colloidal structure and stabilization mechanism of aqueous solutions of unmodified fullerene C60

Despite the inability of fullerenes to be directly dissolved in water, there are methods for preparing stable dispersions of fullerenes in water without any particular modifications of the fullerene or addition of stabilizers. The colloidal properties of such systems prepared by replacing the solvent and structural changes in them during coagulation have been studied. The coagulation dynamics has been investigated by spectroscopy and small-angle neutron scattering. The results obtained confirm the colloidal nature of such systems. During coagulation, particles retain a large volume of water around them, an indication of interaction between fullerene and water during solution stabilization.

C60 fullerene as promising therapeutic agent for correcting and preventing skeletal muscle fatigue

BackgroundBioactive soluble carbon nanostructures, such as the C60 fullerene can bond with up to six electrons, thus serving by a powerful scavenger of reactive oxygen species similarly to many natural antioxidants, widely used to decrease the muscle fatigue effects. The aim of the study is to define action of the pristine C60 fullerene aqueous colloid solution (C60FAS), on the post-fatigue recovering of m. triceps surae in anaesthetized rats.ResultsDuring fatigue development, we observed decrease in the muscle effort level before C60FAS administration. After the application of C60FAS, a slower effort decrease, followed by the prolonged retention of a certain level, was recorded. An analysis of the metabolic process changes accompanying muscle fatigue showed an increase in the oxidative stress markers H2O2 (hydrogen peroxide) and TBARS (thiobarbituric acid reactive substances) in relation to the intact muscles. After C60FAS administration, the TBARS content and H2O2 level were decreased. The endogenous antioxidant system demonstrated a similar effect because the GSH (reduced glutathione) in the muscles and the CAT (catalase) enzyme activity were increased during fatigue.ConclusionsC60FAS leads to reduction in the recovery time of the muscle contraction force and to increase in the time of active muscle functioning before appearance of steady fatigue effects. Therefore, it is possible that C60FAS affects the prooxidant-antioxidant muscle tissue homeostasis, subsequently increasing muscle endurance.

Absorption Characteristics of Fullerene C 60 in N-Methyl-2-Pirrolidone/Toluene Mixture

UV-Vis spectra of fullerene C60 in various mixtures of polar N-methyl-2-pyrrolidone (NMP), ϵ = 32, and low-polar toluene, ϵ = 2.4, are analyzed. A sharp solvatochromic effect is observed when toluene is added to C60/NMP. The comparison with the effect of water addition, ϵ = 80, to C60/NMP is given.

Study of the complexation between Landomycin A and C60 fullerene in aqueous solution

We report here the first investigation of the non-covalent complexation between C60 fullerene and angucycline antibiotic Landomycin A. By means of various physico-chemical methods, including atomic force microscopy, dynamic light scattering, ζ-potential, small-angle neutron scattering and molecular modelling, it was shown that the obtained experimental data indirectly evidence complexation. This result provides scientific reasoning for further examination of the possible biological interaction between these agents on simultaneous administration in vivo and in vitro.

Does C 60 fullerene act as a transporter of small aromatic molecules

C60 fullerene is reported to directly interact with biomolecules, such as aromatic mutagens or anticancer drugs. Therefore, it is extensively studied for its potential application in the fields of drug delivery and chemoprevention. Understanding the nature of fullerene-drugs interactions might contribute to optimization and modification of the existing chemotherapy systems. Possible interactions between ICR-191, a model acridine mutagen, with well-established biophysical properties and mutagenic activity, and C60 fullerene aqueous solution were investigated by broad range of biophysical methods, such as Dynamic Light Scattering, Isothermal Titration Calorimetry, and Atomic Force Microscopy. Additionally, to determine biological activity of ICR-191-C60 fullerene mixtures, Ames mutagenicity test was employed. It was demonstrated that C60 fullerene interacts non-covalently with ICR-191 and has strong affinity to bacterial membranes. The obtained results provide practical insight into C60 fullerene interactions with aromatic compounds.

Self-Organization of Pristine C 60 Fullerene and its Complexes with Chemotherapy Drugs in Aqueous Solution as Promising Anticancer Agents

The self-organization of pristine C60 fullerene and its complexation with chemotherapy drugs (in particular, doxorubicin, cisplatin and landomycin A) in aqueous solution were reviewed as a possible key stage of the mechanism of the in vivo and in vitro biological synergy, observed when these drugs are administered along with C60 fullerene. The results of application of various physico-chemical methods have been analyzed enabling to get insight into the nature of forces stabilizing complexes of C60 fullerene with these drugs. A physico-chemical mechanism has been proposed allowing, at least in part, to explain the C60-drug biological interaction.