TY - JOUR
T1 - Covalent conjugates based on nanodiamonds with doxorubicin and a cytostatic drug from the group of 1,3,5-triazines:
T2 - Synthesis, biocompatibility and biological activity
AU - Sharoyko, Vladimir V
AU - Berdichevsky, Grigory M
AU - Vasina, Lubov V
AU - Shemchuk, Olga S
AU - Maystrenko, Dmitriy N
AU - Molchanov, Oleg E
AU - Abdelhalim, Abdelsattar O E
AU - Nashchekin, Alexey V
AU - Nerukh, Dmitry A
AU - Tochilnikov, Grigorii V
AU - Murin, Igor V
AU - Semenov, Konstantin N
N1 - Copyright © 2023. Published by Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
PY - 2023/9
Y1 - 2023/9
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. [Abstract copyright: Copyright © 2023. Published by Elsevier B.V.]
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. [Abstract copyright: Copyright © 2023. Published by Elsevier B.V.]
KW - Antiradical activity
KW - Biocompatibility
KW - 1,3,5-triazine
KW - Hemocompatibility
KW - Doxorubicin
KW - Nanodiamond
KW - Cytotoxicity
KW - Endocytosis
UR - https://www.sciencedirect.com/science/article/pii/S030441652300082X
UR - http://www.scopus.com/inward/record.url?scp=85161311413&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2023.130384
DO - 10.1016/j.bbagen.2023.130384
M3 - Article
C2 - 37209777
SN - 0304-4165
VL - 1867
SP - 130384
JO - BBA - General Subjects
JF - BBA - General Subjects
IS - 9
ER -