Chemmedchem 2014-06-01

Anti-proliferative activity of nano-formulated phenolato titanium(IV) complexes against cancer cells.

Sigalit Meker, Katrin Margulis-Goshen, Ester Weiss, Ori Braitbard, Jacob Hochman, Shlomo Magdassi, Edit Y Tshuva

Index: ChemMedChem 9(6) , 1294-8, (2014)

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Abstract

Nanoparticles of titanium(IV) complexes of phenolato ligands were formed and evaluated for cytotoxicity toward human HT-29 colon cancer, murine T-25 lymphoma, and murine HU-2 multidrug-resistant (MDR) cells. The nano-formulation, besides increasing the complexes' shelf lives, is particularly efficient in overcoming limitations in solubility and cell-penetration, thus enhancing biological accessibility; large complexes that were inactive when measured in a non-formulated form showed marked activity when nano-formulated. For active and accessible small complexes, the effect of the formulation was negligible. Most complexes showed similar activity toward MDR cells and their drug-sensitive analogues, further increasing their therapeutic potential. An exception is a particularly hydrophobic complex, which is presumably more accessible to interaction with the membrane ABCB1 (MDR1) transporter active in the multidrug resistance of HU-2 cells. The most efficient compound is a mononuclear complex of a single hexadentate ligand, combining particularly high activity and hydrolytic stability with accessibility aided by the nano-formulation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.