TY - JOUR
T1 - Anti-proliferative activity of nano-formulated phenolato titanium(IV) complexes against cancer cells
AU - Meker, Sigalit
AU - Margulis-Goshen, Katrin
AU - Weiss, Ester
AU - Braitbard, Ori
AU - Hochman, Jacob
AU - Magdassi, Shlomo
AU - Tshuva, Edit Y.
PY - 2014/6
Y1 - 2014/6
N2 - 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. A nano-boost for the big: Titanium(IV) complexes of phenolato ligands were analyzed as synthesized and in nano-formulation and showed high cytotoxicity toward human and murine drug-sensitive and -resistant cells. The nano-formulation is highly efficient in improving the biological accessibility of particularly bulky complexes.
AB - 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. A nano-boost for the big: Titanium(IV) complexes of phenolato ligands were analyzed as synthesized and in nano-formulation and showed high cytotoxicity toward human and murine drug-sensitive and -resistant cells. The nano-formulation is highly efficient in improving the biological accessibility of particularly bulky complexes.
KW - cytotoxicity
KW - metallodrugs
KW - multidrug resistance
KW - nano-formulation
KW - titanium(IV)
UR - http://www.scopus.com/inward/record.url?scp=84901508390&partnerID=8YFLogxK
U2 - 10.1002/cmdc.201400038
DO - 10.1002/cmdc.201400038
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C2 - 24677761
AN - SCOPUS:84901508390
SN - 1860-7179
VL - 9
SP - 1294
EP - 1298
JO - ChemMedChem
JF - ChemMedChem
IS - 6
ER -