Examinando por Autor "Fischer-Fodor, Eva"

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    Ítem
    Modulation of the mechanism of apoptosis in cancer cell lines by treatment with silica-based nanostructured materials functionalized with different metallodrugs
    (Royal Society of Chemistry, 2018-08-10) Díaz-García, Diana; Cenariu, Diana; Pérez, Yolanda; Cruz, Paula; del Hierro, Isabel; Prashar, Sanjiv; Fischer-Fodor, Eva; Gómez-Ruiz, Santiago
    The mesoporous silica-based material SBA-15 (Santa Barbara Amorphous-15) has been modified with the aminodiol ligand 3-[bis(2-hydroxyethyl)amino]propyltriethoxysilane (PADOH) to give the corresponding material SBA-PADOH. Subsequent functionalization with a diorganotin(IV) compound, SnPh2Cl2 (1), and with two titanocene derivatives, TiCp2Cl2 ([Ti(η5-C5H5)2Cl2] (2)) and TiCpCpPhNfCl2 ([Ti(η5-C5H5) (η5-C5H4CHPhNf)Cl2] (3) (Ph = C6H5; Nf = C10H7)), gave the materials SBA-PADO-SnPh2 (M1), SBA-PADO-TiCp2 (M2) and SBA-PADO-TiCpCp* (M3), respectively. SBA-PADOH and M1–M3 have been characterized by various techniques such as FT-IR, XRD, XRF, solid-state NMR, nitrogen adsorption– desorption isotherms, electrochemical methods, SEM and TEM, observing that the functionalization has mainly taken place inside the pores of the corresponding porous system. In addition, mechanistic aspects of the apoptosis triggered by the synthesized materials have been studied in vitro in tumour cell lines derived from three distinct types of cancer in order to elucidate their growth inhibition and interference with the expression of tumour necrosis factor alfa (TNF-α) and the first apoptosis signal receptor (Fas or tumour necrosis factor receptor 6). It was observed that the antiproliferative and proapoptotic capacity of the materials depends on their functionalization with the different cytotoxic prodrugs (organotin or titanocene derivatives). The study shows that M1–M3 influence the metabolic activity of the tumour cells and modulate the apoptotic pathways by different mechanisms, according to the active compound inside the material.
  • Miniatura
    Ítem
    Study of cancer cell cytotoxicity, internalization and modulation of growth factors induced by transferrin-conjugated formulations of metallodrug-functionalized mesoporous silica nanoparticles
    (Elsevier, 2021) Díaz-García, Diana; Fischer-Fodor, Eva; Vlad, Cătălin Ioan; Méndez-Arriaga, José M.; Prashar, Sanjiv; Gómez-Ruiz, Santiago
    Nano-sized materials have shown to have very high potential in anticancer therapy by an adequate tuning of their functionalization and physico-chemical properties. This study is focused on the synthesis and characterization of mesoporous silica nanoparticles (MSN) functionalized with a titanium(IV) or an organotin(IV) compound (therapeutic agents), fluorescein isothiocyanate (image agent) and transferrin (targeting molecule). The analysis of the biological activity of the metallodrug-functionalized systems with and without transferrin has been evaluated and the cell internalization with respect to the presence of the protein has been assessed. The biological results show, as expected, that Sn-based materials are more active than the Ti-based systems with some of the tin-functionalized nanoparticles being almost 50 times more active than carboplatin. In contrast, the cellular uptake seems to be higher in Ti-based materials, which take advantage of the stronger interaction with transferrin to internalize the cells with more effectivity. Finally, a study of vascular endothelial growth factor A (VEGF-A), human fibroblast growth factor 2 (FGF-2) and nuclear factor κβ transcription factor (NF-κβ) show that, specially the Sn-based MSNs, were able to modulate these factors in A2780 cells showing anti-angiogenic effects through VEGF-A and FGF-2, probably due to interaction of the materials with transferrin.