A New Generation of Anticancer Drugs: Mesoporous Materials Modified with Titanocene Complexes

Abstract

Dehydroxylated MCM-41 and SBA-15 surfaces were modified by the grafting of two different titanocene complexes ([Ti(eta(5)-C(5)H(4)Me)(2)Cl(2)] and [Ti{Me(2)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)]) to give new materials, which have been characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, MAS-NMR spectroscopy, thermogravimetry, SEM, and TEM. The toxicity of the resulting materials toward human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x, and normal immunocompetent cells, such as peripheral blood mononuclear cells PBMC has been studied. Estimation of the number of particles per gram of material led to the calculation of Q(50) values for these samples, which is the number of particles required to inhibit normal cell growth by 50%. In addition, M(50) values (quantity of material needed to inhibit normal cell growth by 50%) of the studied surfaces is also reported. Nonfunctionalized MCM-41 and SBA-15 did not show notable antiproliferative activity, whereas functionalization of these materials with different titanocene based anticancer drugs led to very promising antitumoral activity. The best Q(50) values correspond to titanocene functionalized MCM-41 surfaces (MCM-41/[Ti(eta(5)-C(5)H(4)Me)(2)Cl(2)] (1) and MCM-41/[Ti{Me(2)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)] (2)) with Q(50) values between 3.8+/-0.6x10(8) and 24.5+/-3.0x10(8) particles. Titanocene functionalized SBA-15 surfaces (SBA-15/[Ti(eta(5)-C(5)H(4)Me)(2)Cl(2)] (3) and SBA-15/[Ti{Me(2)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)] (4)) gave higher Q(50) values, showing lower activity from 73.2+/-9.9x10(8) to 362+/-7x10(8) particles. The best response of the studied materials in terms of M(50) values was observed against Fem-x (309+/-42 microg for 4) and K562 (338+/-18 microg for 2), whereas moderate activities were observed in HeLa cells (from 508+/-63 microg of 2 to 912+/-10 microg of 1). In addition, the analyzed surfaces presented only marginal activity against unstimulated and stimulated PBMC, showing a slight selectivity on human cancer cells. Comparison of the in vitro cytotoxicity in solution of the titanocene complexes [Ti(eta(5)-C(5)H(4)Me)(2)Cl(2)] and [Ti{Me(2)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)] and the corresponding titanocene functionalized materials is also described.

Anticancer activity of dinuclear gallium(III) carboxylate complexes

“…Following our research on the synthesis, characterization and cytotoxic properties of metal-based anticancer drugs [47][48][49][50][51], and encouraged by the good results observed for analogous tin(IV) complexes bearing the same carboxylato ligands [48], we present the synthesis, characterization and study of the cytotoxic activity of different dimeric gallium(III) carboxylate complexes.…”

Organotin(IV)‐Loaded Mesoporous Silica as a Biocompatible Strategy in Cancer Treatment

“…On the other hand, treatment of cells with SBA15pSn (3.85 % Sn) resulted in a remarkable decrease of cell viability (M 50 = 2 mg mL À1 from MTT and 2.6 mg mL À1 from CV assay). The advantage of the novel SBA-15pSn over the most active titanium-loaded mesoporous material (SBA-15 loaded with the [Ti{Me 2 Si(h 5 -C 5 Me 4 )(h 5 -C 5 H 4 )}Cl 2 ], M 50 = 309 AE 42 mg mL À1 ) from the previous study, [14] is that its in vitro activity is more than 150 times higher.…”

“…[14] In the current study, we selected SBA-15 mesoporous silica as a carrier, because of its higher cytotoxicity upon loading with titanium compounds (compared to that of MCM-41 loaded with titanium compounds). [14] Because triphenyltin(IV) compounds express high activities (compared both to titanocene derivatives and cisplatin), [14,15] we present here the strong therapeutic potential of the nanostructured material SBA-15 loaded with an organotin(IV) compound.…”

“…[14] SBA-15p particles were prepared by covalent grafting of SBA-15 with 3-chloropropyltriethoxysilane (CPTS). The extent of the functionalization with attached Si(CH 2 ) 3 Cl units was calculated from the chlorine content (XRF) as 0.76 mmol Cl per g SiO 2 .…”

Anticancer Applications and Recent Investigations of Metallodrugs Based on Gallium, Tin and Titanium

“…Therefore, the anticancer action of these compounds is usually due to decomposition products which are soluble in water and/or DMSO and that are formed after the elimination of one or more ligands [70]. Thus, we focused on the formulation of these titanium derivatives via functionalization of mesoporous silica-based nanostructured materials such as MCM-41, SBA-15, MSU-2, alumina or hydroxyapatite [71][72][73][74] in order to overcome the problems associated with the low hydrolytic stability of titanocene compounds.…”