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A New Generation of Anticancer Drugs: Mesoporous Materials Modified with Titanocene Complexes
Author(s) -
PérezQuintanilla Damian,
GómezRuiz Santiago,
Žižak Željko,
Sierra Isabel,
Prashar Sanjiv,
del Hierro Isabel,
Fajardo Mariano,
Juranić Zorica D.,
Kaluđerović Goran N.
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200900151
Subject(s) - grafting , hela , thermogravimetry , mcm 41 , nuclear chemistry , surface modification , chemistry , mesoporous silica , sorption , cancer cell , mesoporous material , materials science , organic chemistry , in vitro , cancer , biochemistry , inorganic chemistry , adsorption , medicine , catalysis , polymer
The next generation : The grafting of titanocene complexes on the surfaces of MCM‐41 and SBA‐15 led to a new generation of anticancer drugs, which are very active against human cancer cells.Dehydroxylated MCM‐41 and SBA‐15 surfaces were modified by the grafting of two different titanocene complexes ([Ti(η 5 ‐C 5 H 4 Me) 2 Cl 2 ] and [Ti{Me 2 Si(η 5 ‐C 5 Me 4 )(η 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(η 5 ‐C 5 H 4 Me) 2 Cl 2 ] ( 1 ) and MCM‐41/[Ti{Me 2 Si(η 5 ‐C 5 Me 4 )(η 5 ‐C 5 H 4 )}Cl 2 ] ( 2 )) with Q 50 values between 3.8±0.6×10 8 and 24.5±3.0×10 8 particles. Titanocene functionalized SBA‐15 surfaces (SBA‐15/[Ti(η 5 ‐C 5 H 4 Me) 2 Cl 2 ] ( 3 ) and SBA‐15/[Ti{Me 2 Si(η 5 ‐C 5 Me 4 )(η 5 ‐C 5 H 4 )}Cl 2 ] ( 4 )) gave higher Q 50 values, showing lower activity from 73.2±9.9×10 8 to 362±7×10 8 particles. The best response of the studied materials in terms of M 50 values was observed against Fem‐x (309±42 μg for 4 ) and K562 (338±18 μg for 2 ), whereas moderate activities were observed in HeLa cells (from 508±63 μg of 2 to 912±10 μg 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(η 5 ‐C 5 H 4 Me) 2 Cl 2 ] and [Ti{Me 2 Si(η 5 ‐C 5 Me 4 )(η 5 ‐C 5 H 4 )}Cl 2 ] and the corresponding titanocene functionalized materials is also described.