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

Molecules

Sigalit Meker³  Ori Braitbard¹  Katrin Margulis-Goshen³  Shlomo Magdassi³  Jacob Hochman¹  Edit Y. Tshuva³  Thomas Rades²  Holger Grohganz² 

[1] Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem 91904, Israel; E-Mails:The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel;;The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel; E-Mails:

关键词: titanium(IV);    phenolato ligands;    cisplatin;    cytotoxicity;    anti-tumor;    cisplatin resistant cells;   

DOI  :  10.3390/molecules201018526

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.