Platinum Polyoxoniobate: Stability, Cytotoxicity, and Cellular Uptake

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: Quantum 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.