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Molecules 2015, 20(10), 18526-18538; doi:10.3390/molecules201018526

Highly Stable Tetra-Phenolato Titanium(IV) Agent Formulated into Nanoparticles Demonstrates Anti-Tumoral Activity and Selectivity

1
The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
2
Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
*
Author to whom correspondence should be addressed.
Academic Editors: Thomas Rades, Holger Grohganz and Korbinian Löbmann
Received: 1 September 2015 / Revised: 30 September 2015 / Accepted: 5 October 2015 / Published: 9 October 2015
(This article belongs to the Collection Poorly Soluble Drugs)
View Full-Text   |   Download PDF [847 KB, uploaded 9 October 2015]   |  

Abstract

Titanium(IV) complexes exhibit high potential as anti-tumor agents, particularly due to their low intrinsic toxicity and cytotoxicity toward cisplatin resistant cells. Nevertheless, Ti(IV) complexes generally undergo rapid hydrolysis that previously hampered their utilization as anticancer drugs. We recently overcame this difficulty by developing a highly stable Ti(IV) complex that is based on tetra-phenolato, hexadentate ligand, formulated into organic nanoparticles. Herein we investigated the activity of this complex in vitro and in vivo. Although inactive when tested directly due to poor solubility, when formulated, this complex displayed (a) high cytotoxicity toward cisplatin resistant human ovarian cells, A2780-cp, with resistance factor of 1.1; (b) additive behavior in combination with cisplatin toward ovarian and colon cancer cells; (c) selectivity toward cancer cells as implied by its mild activity toward non-cancerous, fibroblast lung cells, MRC-5; (d) high stability and durability as manifested by the ability to maintain cytotoxicity, even following one week of incubation in 100% aquatic medium solution; and (e) in vivo efficacy toward solid tumors of human colon cancer cells, HT-29, in nude mice without any clinical signs of toxicity. These features support the formulated phenolato Ti(IV) complex being an effective and selective anti-tumoral agent. View Full-Text
Keywords: titanium(IV); phenolato ligands; cisplatin; cytotoxicity; anti-tumor; cisplatin resistant cells titanium(IV); phenolato ligands; cisplatin; cytotoxicity; anti-tumor; cisplatin resistant cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Meker, S.; Braitbard, O.; Margulis-Goshen, K.; Magdassi, S.; Hochman, J.; Tshuva, E.Y. Highly Stable Tetra-Phenolato Titanium(IV) Agent Formulated into Nanoparticles Demonstrates Anti-Tumoral Activity and Selectivity. Molecules 2015, 20, 18526-18538.

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