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Materials 2018, 11(2), 224; https://doi.org/10.3390/ma11020224

Anticancer Applications of Nanostructured Silica-Based Materials Functionalized with Titanocene Derivatives: Induction of Cell Death Mechanism through TNFR1 Modulation

1
Departamento de Biología y Geología, Física y Química Inorgánica, ESCET, Universidad Rey Juan Carlos, Calle Tulipán s/n, E-28933 Móstoles (Madrid), Spain
2
College of Materials Science and Engineering, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, Nanshan District Key Laboratory for Biopolymers and Safety Evaluation, Shenzhen University, Shenzhen 518060, China
3
Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China
4
Departamento de Química Inorgánica, Universidad de Granada, Facultad de Ciencias, Campus de Fuentenueva, Avda. Fuentenueva s/n, E-18071 Granada, Spain
5
Medfuture-Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, RO-400337 Cluj-Napoca, Romania
6
Tumor Biology Department, The Oncology Institute “I. Chiricuta”, RO-400015 Cluj-Napoca, Romania
*
Authors to whom correspondence should be addressed.
Received: 15 November 2017 / Revised: 23 January 2018 / Accepted: 30 January 2018 / Published: 31 January 2018
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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Abstract

A series of cytotoxic titanocene derivatives have been immobilized onto nanostructured silica-based materials using two different synthetic routes, namely, (i) a simple grafting protocol via protonolysis of the Ti–Cl bond; and (ii) a tethering method by elimination of ethanol using triethoxysilyl moieties of thiolato ligands attached to titanium. The resulting nanostructured systems have been characterized by different techniques such as XRD, XRF, DR-UV, BET, SEM, and TEM, observing the incorporation of the titanocene derivatives onto the nanostructured silica and slight changes in the textural features of the materials after functionalization with the metallodrugs. A complete biological study has been carried out using the synthesized materials exhibiting moderate cytotoxicity in vitro against three human hepatic carcinoma (HepG2, SK-Hep-1, Hep3B) and three human colon carcinomas (DLD-1, HT-29, COLO320) and very low cytotoxicity against normal cell lines. In addition, the cells’ metabolic activity was modified by a 24-h exposure in a dose-dependent manner. Despite not having a significant effect on TNFα or the proinflammatory interleukin 1α secretion, the materials strongly modulated tumor necrosis factor (TNF) signaling, even at sub-cytotoxic concentrations. This is achieved mainly by upregulation of the TNFR1 receptor production, something which has not previously been observed for these systems. View Full-Text
Keywords: nanostructured silica; titanocene; cytotoxicity; anticancer; tumor necrosis factor; TNFR1 modulation nanostructured silica; titanocene; cytotoxicity; anticancer; tumor necrosis factor; TNFR1 modulation
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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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Gómez-Ruiz, S.; García-Peñas, A.; Prashar, S.; Rodríguez-Diéguez, A.; Fischer-Fodor, E. Anticancer Applications of Nanostructured Silica-Based Materials Functionalized with Titanocene Derivatives: Induction of Cell Death Mechanism through TNFR1 Modulation. Materials 2018, 11, 224.

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