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.

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.