Study of the cytotoxicity and particle action in human cancer cells of titanocene-functionalized materials with potential application against tumors

摘要

Titanocene dichloride [Ti(η ~5-C _5H _5) _2Cl _2] (1), has been grafted onto dehydrated hydroxyapatite (HAP), Al _2O _3 and two mesoporous silicas MSU-2 (Michigan State University Silica type 2) and HMS (Hexagonal Mesoporous Silica), to give the novel materials HAP/[Ti(η ~5-C _5H _5) _2Cl _2] (S1) (1.01 wt.% Ti), Al _2O _3/[Ti(η ~5-C _5H _5) _2Cl _2] (S2) (2.36 wt.% Ti), HMS/[Ti(η ~5-C _5H _5) _2Cl _2] (S3) (0.75 wt.% Ti) and MSU-2/[Ti(η ~5-C _5H _5) _2Cl _2] (S4) (0.74 wt.% Ti), which have been characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, multinuclear magic angle spinning NMR spectroscopy, IR spectroscopy, thermogravimetry analysis, UV spectroscopy, scanning electronic microscopy and transmission electronic microscopy. The cytotoxicity of the titanocene-functionalized materials toward human cancer cell lines from five different histogenic origins: 8505 C (anaplastic thyroid cancer), A253 (head and neck cancer), A549 (lung carcinoma), A2780 (ovarian cancer) and DLD-1 (colon cancer) has been determined. M _(50) values (quantity of material needed to inhibit normal cell growth by 50%) and Ti-M _(50) values (quantity of anchored titanium needed to inhibit normal cell growth by 50%) indicate that the activity of S1-S4 against studied human cancer cells depended on the surface type as well as on the cell line. In addition, studies on the titanocene release and the interaction of the materials S1-S4 with DNA show that the cytotoxic activity may be due to particle action, because no release of titanium complexes has been observed in physiological conditions, while electrostatic interactions of titanocene-functionalized particles with DNA have been observed.