Novel Photodynamic Therapy Using Water‐dispersed TiO₂–Polyethylene Glycol Compound: Evaluation of Antitumor Effect on Glioma Cells and Spheroids In Vitro

Abstract

Titanium dioxide (TiO(2)) is thought to be a photocatalytic agent excited by UV light. Our aim was to investigate the photocatalytic antitumor effect of water-dispersed TiO(2) nanoparticles on C6 rat glioma cells and to evaluate the treatment responses by the spheroid models. Water-dispersed TiO(2) nanoparticles were constructed by the adsorption of chemical modified polyethylene glycol (PEG) on the TiO(2) surface (TiO(2)/PEG). Each monolayer and spheroid of C6 cells was coincubated with various concentrations of TiO(2)/PEG and subsequently irradiated with UV light. Damage of the cells and spheroids was evaluated sequentially by staining with the fluorescent dyes. The cytotoxic effect was correlated with the concentration of TiO(2)/PEG and the energy dose of UV irradiation. More than 90% of cells were killed after 13.5 J cm(-2) of UV irradiation in the presence of 500 microg mL(-1) TiO(2)/PEG. The irradiated spheroids in the presence of TiO(2)/PEG showed growth suppression compared with control groups. In TiO(2)/PEG-treated spheroids, the number of Annexin V-FITC-stained cells gradually increased during the first 6 h, and subsequently propidium iodide-stained cells appeared. The results of this study suggest that newly developed photoexcited TiO(2)/PEG have antitumoral activity. Photodynamic therapy utilizing this material can be a clue to a novel therapeutic strategy for glioma.

Sonodynamic therapy using water-dispersed TiO2-polyethylene glycol compound on glioma cells: Comparison of cytotoxic mechanism with photodynamic therapy

“…Hydrophilicity can be an important property of cell permeability of sensitizers [13], and TiO 2 /PEG nanoparticles have colloidal stabilization and dispersibility in aqueous solution. Our previous investigations have shown that these nanoparticles might attach to tumor cell membranes and be incorporated in tumor cells [32]. This experimental result indicated that the water dispersed TiO 2 /PEG exists in close vicinity of the cell membrane.…”

“…We have developed a novel water-dispersed TiO 2 nanoparticle modified by polyethylene glycole (PEG) and demonstrated its photocatalytic anti-tumor effect on a glioma cell line [32]. These nanoparticle compounds are approximately 50 nm in diameter, and their dispersion and stability in an aqueous medium have been confirmed.…”

Tailoring the interplay between electromagnetic fields and nanomaterials toward applications in life sciences: a review

“…187,188 To date, light activation of TiO 2 NPs represents a major safety concern for nanotoxicology rather than a therapeutic opportunity, 185 although some reports exist. [189][190][191] Equivalent to common photosensitizers, QDs have also been proposed as intrinsic PDT agents. [192][193][194] However, the QYs of the singlet oxygen of QDs are very low compared to the ones of common photosensitizers (ca.…”

Three-Dimensional In Vitro Models in Glioma Research - Focus on Spheroids

“…The amount of formazan produced is directly proportional to the amount of LDH in the culture medium, which in turn is directly proportional to the number of dead or damaged cells (Korzeniewski & Callewaert, 1983). The size of spheroids after drug treatment has also been used as a measure of cell viability (Fehlauer et al, 2007;Johannessen et al, 2009;Khaitan et al, 2009;Yamaguchi et al, 2010). Khaitan et al (Khaitan et al, 2009) investigated the effect of the glycolytic inhibitor 2-deoxy-D-glucose on spheroids derived from a human glioma cell line by measuring the size of the spheroids after drug exposure.…”