TY - JOUR

T1 - Covalent conjugates based on nanodiamonds with doxorubicin and a cytostatic drug from the group of 1,3,5-triazines: Synthesis, biocompatibility and biological activity

AU - Шаройко, Владимир Владимирович

AU - Berdichevsky, G. M.

AU - Vasina,, L. V.

AU - Шемчук, Ольга Сергеевна

AU - Maystrenko, , D. N.

AU - Molchanov, O. E.

AU - Абделхалим, Абделсаттар Осама Елемам

AU - Nashchekin, A. V.

AU - Nerukh, , D. A.

AU - Tochilnikov, G. V

AU - Мурин, Игорь Васильевич

AU - Семёнов, Константин Николаевич

PY - 2023/9/1

Y1 - 2023/9/1

N2 - 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.

AB - 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.

KW - 1,3,5-triazine

KW - Antiradical activity

KW - Biocompatibility

KW - Cytotoxicity

KW - Doxorubicin

KW - Endocytosis

KW - Hemocompatibility

KW - Nanodiamond

UR - https://www.mendeley.com/catalogue/c6a12d3c-1964-3afd-987b-0356e581e10e/

U2 - 10.1016/j.bbagen.2023.130384

DO - 10.1016/j.bbagen.2023.130384

M3 - статья

VL - 1867

JO - Biochimica et Biophysica Acta - General Subjects

JF - Biochimica et Biophysica Acta - General Subjects

SN - 0006-3002

IS - 9

M1 - 130384

ER -