title: Anti-proliferative activity of nano-formulated phenolato titanium(IV) complexes against cancer cells.
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.
authors.affiliation: The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel).
authors.forename: Sigalit
authors.initials: S
authors.lastname: Meker
authors.forename: Katrin
authors.initials: K
authors.lastname: Margulis-Goshen
authors.forename: Ester
authors.initials: E
authors.lastname: Weiss
authors.forename: Ori
authors.initials: O
authors.lastname: Braitbard
authors.forename: Jacob
authors.initials: J
authors.lastname: Hochman
authors.forename: Shlomo
authors.initials: S
authors.lastname: Magdassi
authors.forename: Edit Y
authors.initials: EY
authors.lastname: Tshuva
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003110:Colonic Neoplasms; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D036103:Nanotechnology; D014025:Titanium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D014025:Titanium
keywords: cytotoxicity; metallodrugs; multidrug resistance; nano-formulation; titanium(IV)