TY - JOUR

T1 - Platinum Polyoxoniobate: Stability, Cytotoxicity, and Cellular Uptake

AU - Yudkina, A V

AU - Vokhtantsev, I P

AU - Rychkov, D A

AU - Volchek, V V

AU - Abramov, P A

AU - Sokolov, M. N.

AU - Zharkov, D. O.

N1 - The study was supported by the Russian Foundation for Basic Research and the Government of the Novosibirsk Region (grant r_mol_a 19-44-543011) and the state assignment of the Synchrotron Radiation Facility – Siberian Circular Photon Source “SKIF” (FWUR-2024-0040).

PY - 2025/4/6

Y1 - 2025/4/6

N2 - Abstract—Objective: Platinum polyoxometalates are Pt (IV) complexes containing bulky cluster ligands. We have shown previously that platinum polyoxoniobate [(Nb6O19)2{Pt(OH)2}2]12− (Pt-PON1) containing two Pt centers can covalently bind DNA. Here we have addressed the structural stability of Pt-PON1 and its conjugate with guanine at the N7 position, cytotoxicity of this compound, and its accumulation in living cells. Methods: Quan- tum mechanical modeling was used to estimate the stability of Pt–guanine bond. Cytotoxicity of Pt-PON1 was evaluated by incubating various concentrations of the compound with cultured human and Escherichia coli cells, and the levels of intracellular Pt-PON1, by atomic emission spectroscopy. Results and Discussion: Calculations show that the Pt-PON1 complex is unstable outside the crystal lattice, while its conjugate with guanine likely undergoes structural rearrangement quite easily. A decrease in the survival of E. coli XL1-Blue and DH5α strains and human HEK293T and MCF-7 cell lines was observed already at 20 μM Pt-PON1 but at higher concentrations the compound was poorly soluble in biologically compatible media. The measured levels of intracellular Pt and Nb suggest that Pt-PON1 is efficiently taken up by human cells in a stoichiometry corresponding to the original complex. Conclusions: Platinum polyoxometalates, provided their solubility can be improved, may be considered as promising antitumor agents.

AB - Abstract—Objective: Platinum polyoxometalates are Pt (IV) complexes containing bulky cluster ligands. We have shown previously that platinum polyoxoniobate [(Nb6O19)2{Pt(OH)2}2]12− (Pt-PON1) containing two Pt centers can covalently bind DNA. Here we have addressed the structural stability of Pt-PON1 and its conjugate with guanine at the N7 position, cytotoxicity of this compound, and its accumulation in living cells. Methods: Quan- tum mechanical modeling was used to estimate the stability of Pt–guanine bond. Cytotoxicity of Pt-PON1 was evaluated by incubating various concentrations of the compound with cultured human and Escherichia coli cells, and the levels of intracellular Pt-PON1, by atomic emission spectroscopy. Results and Discussion: Calculations show that the Pt-PON1 complex is unstable outside the crystal lattice, while its conjugate with guanine likely undergoes structural rearrangement quite easily. A decrease in the survival of E. coli XL1-Blue and DH5α strains and human HEK293T and MCF-7 cell lines was observed already at 20 μM Pt-PON1 but at higher concentrations the compound was poorly soluble in biologically compatible media. The measured levels of intracellular Pt and Nb suggest that Pt-PON1 is efficiently taken up by human cells in a stoichiometry corresponding to the original complex. Conclusions: Platinum polyoxometalates, provided their solubility can be improved, may be considered as promising antitumor agents.

KW - cytotoxicity

KW - dna damage

KW - platinum-based drugs

KW - polyoxometallates

UR - https://link.springer.com/10.1134/S1068162024606141

UR - https://www.mendeley.com/catalogue/1678cf89-3bcc-3ea7-b4cb-15e8daa2cdce/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-105003017423&origin=inward&txGid=c847ec165a1e95e55b0fc2c8778af4a0

U2 - 10.1134/S1068162024606141

DO - 10.1134/S1068162024606141

M3 - Article

VL - 51

SP - 693

EP - 701

JO - Russian Journal of Bioorganic Chemistry

JF - Russian Journal of Bioorganic Chemistry

SN - 1068-1620

IS - 2

ER -