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Anti‐proliferative Activity of Nano‐Formulated Phenolato Titanium(IV) Complexes Against Cancer Cells
Author(s) -
Meker Sigalit,
MargulisGoshen Katrin,
Weiss Ester,
Braitbard Ori,
Hochman Jacob,
Magdassi Shlomo,
Tshuva Edit Y.
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201400038
Subject(s) - chemistry , cytotoxicity , cancer cell , multiple drug resistance , ligand (biochemistry) , transporter , combinatorial chemistry , in vitro , cancer , biochemistry , receptor , biology , gene , genetics , antibiotics
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.