In Vitro Studies Demonstrate Antitumor Activity of Vanadium Ions from a CaO-P2O5-CaF2:V2O5 Glass System in Human Cancer Cell Lines A375, A2780, and Caco-2.

In this research, we investigated the structural and biological properties of phosphate glasses (PGs) after the addition of V2O5. A xV2O5∙(100 − x)[CaF2∙3P2O5∙CaO] glass system with 0 ≤ x ≤ 16 mol% was synthesized via a conventional melt-quenching technique. Several analysis techniques (dissolution tests, pH, SEM-EDS, FT-IR, and EPR) were used to obtain new experimental data regarding the structural behavior of the system. In vitro tests were conducted to assess the antitumor character of V2O5-doped glass (x = 16 mol%) compared to the matrix (x = 0 mol%) and control (CTRL-) using several tumoral cell lines (A375, A2780, and Caco-2). The characterization of PGs showed an overall dissolution rate of over 90% for all vitreous samples (M and V1−V7) and the high reactivity of this system. EPR revealed a well-resolved hyperfine structure (hfs) typical of vanadyl ions in a C4v symmetry. FT-IR spectra showed the presence of all structural units expected for P2O5, as well as very clear depolymerization of the vitreous network induced by V2O5. The MTT assay indicated that the viability of tumor cells treated with V7-glass extract was reduced to 50% when the highest concentration was used (10 µg/mL) compared to the matrix treatment (which showed no cytotoxic effect at any concentration). Moreover, the matrix treatment (without V2O5) provided an optimal environment for tumor cell attachment and proliferation. In conclusion, the two types of treatment investigated herein were proven to be very different from a statistical point of view (p < 0.01), and the in vitro studies clearly underline the cytotoxic potential of vanadium ions from phosphate glass (V7) as an antitumor agent.

A Fast, Reliable Oil-In-Water Microemulsion Procedure for Silica Coating of Ferromagnetic Zn Ferrite Nanoparticles Capable of Inducing Cancer Cell Death In Vitro.

The applications of ferrimagnetic nanoparticles (F-MNPs) in magnetic hyperthermia (MH) are restricted by their stabilization in microscale aggregates due to magnetostatic interactions significantly reducing their heating performances. Coating the F-MNPs in a silica layer is expected to significantly reduce the magnetostatic interactions, thereby increasing their heating ability. A new fast, facile, and eco-friendly oil-in-water microemulsion-based method was used for coating Zn0.4Fe2.6O4 F-MNPs in a silica layer within 30 min by using ultrasounds. The silica-coated clusters were characterized by various physicochemical techniques and MH, while cytotoxicity studies, cellular uptake determination, and in vitro MH experiments were performed on normal and malignant cell lines. The average hydrodynamic diameter of silica-coated clusters was approximately 145 nm, displaying a high heating performance (up to 2600 W/gFe). Biocompatibility up to 250 µg/cm2 (0.8 mg/mL) was recorded by Alamar Blue and Neutral Red assays. The silica-coating increases the cellular uptake of Zn0.4Fe2.6O4 clusters up to three times and significantly improves their intracellular MH performances. A 90% drop in cellular viability was recorded after 30 min of MH treatment (20 kA/m, 355 kHz) for a dosage level of 62.5 µg/cm2 (0.2 mg/mL), while normal cells were more resilient to MH treatment.

Synthesis and Structural Characterization of CaO-P2O5-CaF:CuO Glasses with Antitumoral Effect on Skin Cancer Cells.

Copper is one of the most used therapeutic metallic elements in biomedicine, ranging from antibacterial approaches to developing new complexes in cancer therapy. In the present investigation, we developed a novel xCuO∙(100 - x) [CaF2∙3P2O5∙CaO] glass system with 0 ≤ x ≤ 16 mol% in order to determine the influence of doping on the composition structure of glasses. The samples were characterized by dissolution tests, pH measurements, Fourier-transform infrared spectroscopy (FT-IR), electron paramagnetic resonance (EPR), Scanning Electron Microscopy with energy dispersive spectroscopy (SEM-EDX) and afterward, their antitumor character was assessed. The glasses were mostly soluble in the aqueous medium, their dissolution rate being directly proportional to the increase in pH and the level of doping up to x = 8 mol%. FT-IR spectra of glass samples show the presence of all structural units characteristic to P2O5 in different rates and directly depending on the depolymerization process. SEM-EDX results revealed the presence of an amorphous glass structure composed of P, O, Ca, and Cu elements. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay showed strong cytotoxicity for tumoral cells A375 even in low concentrations for Cu-treatment. In contrast, the copper-free matrix (without Cu) determined a proliferative effect of over 70% viability for all concentrations used.

Silica Coating of Ferromagnetic Iron Oxide Magnetic Nanoparticles Significantly Enhances Their Hyperthermia Performances for Efficiently Inducing Cancer Cells Death In Vitro.

Increasing the biocompatibility, cellular uptake, and magnetic heating performance of ferromagnetic iron-oxide magnetic nanoparticles (F-MNPs) is clearly required to efficiently induce apoptosis of cancer cells by magnetic hyperthermia (MH). Thus, F-MNPs were coated with silica layers of different thicknesses via a reverse microemulsion method, and their morphological, structural, and magnetic properties were evaluated by multiple techniques. The presence of a SiO2 layer significantly increased the colloidal stability of F-MNPs, which also enhanced their heating performance in water with almost 1000 W/gFe as compared to bare F-MNPs. The silica-coated F-MNPs exhibited biocompatibility of up to 250 µg/cm2 as assessed by Alamar Blues and Neutral Red assays on two cancer cell lines and one normal cell line. The cancer cells were found to internalize a higher quantity of silica-coated F-MNPs, in large endosomes, dispersed in the cytoplasm or inside lysosomes, and hence were more sensitive to in vitro MH treatment compared to the normal ones. Cellular death of more than 50% of the malignant cells was reached starting at a dose of 31.25 µg/cm2 and an amplitude of alternating magnetic field of 30 kA/m at 355 kHz.

In Vitro Intracellular Hyperthermia of Iron Oxide Magnetic Nanoparticles, Synthesized at High Temperature by a Polyol Process.

We report the synthesis of magnetite nanoparticles (IOMNPs) using the polyol method performed at elevated temperature (300 °C) and high pressure. The ferromagnetic polyhedral IOMNPs exhibited high saturation magnetizations at room temperature (83 emu/g) and a maximum specific absorption rate (SAR) of 2400 W/gFe in water. The uniform dispersion of IOMNPs in solid matrix led to a monotonous increase of SAR maximum (3600 W/gFe) as the concentration decreased. Cytotoxicity studies on two cell lines (cancer and normal) using Alamar Blues and Neutral Red assays revealed insignificant toxicity of the IOMNPs on the cells up to a concentration of 1000 µg/mL. The cells internalized the IOMNPs inside lysosomes in a dose-dependent manner, with higher amounts of IOMNPs in cancer cells. Intracellular hyperthermia experiments revealed a significant increase in the macroscopic temperatures of the IOMNPs loaded cell suspensions, which depend on the amount of internalized IOMNPs and the alternating magnetic field amplitude. The cancer cells were found to be more sensitive to the intracellular hyperthermia compared to the normal ones. For both cell lines, cells heated at the same macroscopic temperature presented lower viability at higher amplitudes of the alternating magnetic field, indicating the occurrence of mechanical or nanoscale heating effects.