Covalent conjugates based on nanodiamonds with doxorubicin and a cytostatic drug from the group of 1,3,5-triazines: Synthesis, biocompatibility and biological activity.

We report the synthesis of covalent conjugates of nanodiamonds with doxorubicin and a cytostatic drug from the class of 1,3,5-triazines. The obtained conjugates were identified using a number of physicochemical methods (IR-spectroscopy, NMR-spectroscopy, XRD, XPS, TEM). As a result of our study, it was found that ND-СONH-Dox and ND-COO-Diox showed good hemocompatibility, since they did not affect plasma coagulation hemostasis, platelet functional activity, and erythrocyte membrane. The ND-COO-Diox conjugates are also capable of binding to human serum albumin due to the presence of ND in their composition. In the study of the cytotoxic properties of ND-СONH-Dox and ND-COO-Diox in the T98G glioblastoma cell line, indicating that ND-СONH-Dox and ND-COO-Diox demonstrate greater cytotoxicity at lower concentrations of Dox and Diox in the composition of the conjugates compared to individual drugs; the cytotoxic effect of ND-COO-Diox was statistically significantly higher than that of ND-СONH-Dox at all concentrations studied. Greater cytotoxicity at lower concentrations of Dox and Diox in the composition of conjugates compared to individual cytostatics makes it promising to further study the specific antitumor activity and acute toxicity of these conjugates in models of glioblastoma in vivo. Our results demonstrated that ND-СONH-Dox and ND-COO-Diox enter HeLa cells predominantly via a nonspecific actin-dependent mechanism, while for ND-СONH-Dox a clathrin-dependent endocytosis pathway. All data obtained provide that the synthesized nanomaterials show a potential application as the agents for intertumoral administration.

Study of biocompatibility, cytotoxic activity in vitro of a tetrazole-containing derivative of 2-amino-4,6-di(aziridin-1-yl)-1,3,5-triazine.

The hydrolytic stability, hemocompatibility, antioxidant properties and in vitro cytotoxic activity of {5-[(4,6-di(aziridin-1-yl)-1,3,5-triazin-2-yl)amino]-2,2-dimethyl-1,3-dioxan-5-yl}methyl 2-(5-phenyl-2H-tetrazol-2-yl)acetate have been studied. 1H NMR spectroscopy showed that this tetrazole-containing derivative of 1,3,5-triazine is stable in neutral (pH 7) and alkaline (pH 10) media; hydrolysis of the dioxane cycle occurs in an acidic environment (pH 3). It has been established that {5-[(4,6-di(aziridin-1-yl)-1,3,5-triazin-2-yl)amino]-2,2-dimethyl-1,3-dioxan-5-yl}methyl-2-(5-phenyl-2H-tetrazol-2-yl)acetate is hemocompatible, exhibits antioxidant properties, but does not show antiradical activity over the entire range of concentrations. In turn, the study of cytotoxic activity in vitro showed that the tetrazole-containing derivative of 1,3,5-triazine has an effect on the cell lines of human alveolar basal epithelium adenocarcinoma A549 (IC50 41.3 µmol l-1), human ovarian teratocarcinoma PA-1 (IC50 10.6 µmol l-1), hepatocarcinoma Huh7 (IC50 19.9 µmol l-1), cervical cancer HeLa (IC50 3.7 µmol l-1), and human embryonic kidney HEK293 (IC50 15.8 µmol l-1). It was suggested one of the possible mechanism of substance 2 cytotoxicity via HIF pathway inhibition.

Graphene oxide enriched with oxygen-containing groups: on the way to an increase of antioxidant activity and biocompatibility.

The article is dedicated to the comprehensive biocompatibility investigation of synthesised graphene oxide (GO) enriched with oxygen-containing functional groups (⁓85%). GO was synthesised through a modified Hummers and Offeman's method and characterised using 13C NMR, Raman, and IR spectroscopy, XRD, HRTEM, along with size dimensions and ζ-potentials in aqueous dispersions. Biocompatibility study included tests on haemocompatibility (haemolysis, platelet aggregation, binding to human serum albumin and its esterase activity), antioxidant activity (2,2-diphenyl-1-picrylhydrazyl reaction, NO-radical uptake, Radachlorin photobleaching, photo-induced haemolysis), genotoxicity using DNA comet assay, as well as metabolic activity and proliferation of HEK293 cells.

Biocompatibility, antioxidant activity and collagen photoprotection properties of C60 fullerene adduct with L-methionine.

Functionalization of the fullerene core with amino acids has become a new and promising direction in the field of nanochemistry. The biologic activity of water-soluble fullerene derivatives is based on such properties as lipophilicity, electron deficiency and photosensitivity. The complex of above-mentioned properties can be used to develop protection of biomolecules (in particular, proteins) from external physical and chemical influences. Thus, development and up-scaling of synthesis procedures, as well as investigation of the biological properties of these derivatives, are extremely important. This paper presents new data on the biocompatibility studies of C60 fullerene adduct with L-methionine (C60[C5H11NO2S]3; C60-Met). Antiradical activity, binding to human serum albumin (HSA), collagen and deoxyribonucleic acid (DNA), hemocompatibility, photodynamic properties, genotoxicity and cytotoxicity were studied. In addition, it was found that C60-Met increases the photostability of the collagen molecule, and this effect is dose-dependent.

In Vitro and In Silico Investigation of Water-Soluble Fullerenol C60(OH)24: Bioactivity and Biocompatibility.

Light fullerenes, C60 and C70, have significant potential in biomedical applications due to their ability to absorb reactive oxygen species, inhibit the development of tumors, inactivate viruses and bacteria, and as the basis for developing systems for targeted drug delivery. However, the hydrophobicity of individual fullerenes complicates their practical use; therefore, creating water-soluble derivatives of fullerenes is increasingly important. Currently, the most studied soluble adducts of fullerenes are polyhydroxy fullerenes or fullerenols. Unfortunately, investigations of fullerenol biocompatibility are fragmental. They often lack reproducibility both in the synthesis of the compounds and their biological action. We here investigate the biocompatibility of a well-defined fullerenol C60(OH)24 obtained using methods that minimize the content of impurities and quantitatively characterize the product's composition. We carry out comprehensive biochemical and biophysical investigations of C60(OH)24 that include photodynamic properties, cyto- and genotoxicity, hemocompatibility (spontaneous and photo-induced hemolysis, platelet aggregation), and the thermodynamic characteristics of C60(OH)24 binding to human serum albumin and DNA. The performed studies show good biocompatibility of fullerenol C60(OH)24, which makes it a promising object for potential use in biomedicine.

Biocompatibility of a nanocomposite based on Aerosil 380 and carboxylated fullerene C60[C(COOH)2]3.

Silica is silicon dioxide, which, depending on the production method, can exist in various amorphous forms with varying specific surface area, particle size, pore volume and size, and, as a result, with different physicochemical and sorption characteristics. The presence of silanol groups on the surface of silicas provides the possibility of its further functionalisation. In addition, the developed specific surface of Aerosil allows to obtain composites with a high content of biologically active substances. In this work, we studied the biocompatibility of a composite based on Aerosil 380 and carboxylated fullerene C60[C(COOH)2]3, namely: haemolysis (spontaneous and photoinduced), platelet aggregation, binding to HSA, cyto- and genotoxicity, antiradical activity. Interest in the creation of this nanomaterial is due to the fact that carboxylated fullerenes have potential applications in various fields of biomedicine, including the ability to bind reactive oxygen species, inhibition of tumour development, inactivation of viruses and bacteria. The obtained composite can be used for the immobilisation of various drugs and the further development of drugs for theranostics.

Physicochemical properties, biological activity and biocompatibility of water-soluble C60-Hyp adduct.

Amino acid adducts of light fullerenes have a potential of application in a variety of fields of biomedicine, that is reactive oxygen species scavenging activity, anticancer activity, viruses and bacteria inactivation etc. In this work, the water-soluble C60 fullerene derivative with l-hydroxyproline (C60(C5H9NO3)2, C60-Hyp) was studied. Extensive biomedical investigation of this compound, namely, antiradical activity in the reaction with stable diphenylpicrylhydrazyl radical, the binding to human serum albumin, photodynamic properties, cytotoxicity in glioblastoma A172 and lung carcinoma A549 cell lines, erythrocytes haemolysis, platelet aggregation, genotoxicity on human peripheral blood mononuclear cells was conducted. Moreover, the dynamic and structural characteristics of C60-Hyp-H2O binary system were obtained using molecular dynamic (MD) method, and size distribution along with ζ-potentials of C60-Hyp associates was measured.

Reduction and functionalization of graphene oxide with L-cysteine: Synthesis, characterization and biocompatibility.

This article presents data on the synthesis, identification, computer simulation and biocompatibility of graphene oxide (GO) functionalized with L-cysteine (GFC). It was determined that GO reacts with L-cysteine in two different ways: in an alkaline medium, L-cysteine reduces functional groups on the surface and at the boundaries of GO; with heating and the use of thionyl chloride, L-cysteine covalently attaches to GO through carboxylic groups only at the boundaries. The identification of GO, reduced graphene oxide and GFC was performed using various physicochemical methods, including infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, thermogravimetric analysis, scanning electron microscopy and high-resolution transmission electron microscopy. Biocompatibility experiments included erythrocyte hemolysis, platelet aggregation, photodynamic and antiradical activity, binding to human serum albumin, and geno- and cytotoxicity studies. Applying density functional theory and molecular dynamics allowed us to obtain the structural and dynamic characteristics of a GFC-water binary system.

Biological evaluation and molecular dynamics simulation of water-soluble fullerene derivative C60[C(COOH)2]3.

One of the most studied fullerene members, C60, has a potential of application in various fields of biomedicine including reactive oxygen species (ROS) scavenging activity, inhibiting of tumours development, inactivating of viruses and bacteria, as well as elaboration of diagnostic and targeted drug delivery tools. However, the hydrophobicity of this molecule impedes its practical use, therefore the actuality of the research devoted to functionalisation of fullerenes leading to amphiphilic derivatives remains important. In this work, the water-soluble carboxylated fullerene derivative C60[C(COOH)2]3 was studied. Extensive biomedical investigation of this compound, namely, the binding with human serum albumin (HSA), radical scavenging activity in the reaction with diphenylpicrylhydrazyl (DPPH) radical, photodynamic properties, cytotoxicity in human embryonic kidney (HEK293) cell line, erythrocytes' haemolysis, platelet aggregation, and genotoxicity in human peripheral mononuclear cells (PBMC) was conducted. Moreover, the dynamic and structural characteristics of C60[C(COOH)2]3-H2O binary system were obtained using molecular dynamic (MD) method, and size distribution of C60[C(COOH)2]3 associates was measured.