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

被引:131
作者
Yamaguchi, Shigeru
Kobayashi, Hiroyuki
Narita, Takuhito
Kanehira, Koki [2 ]
Sonezaki, Shuji [2 ]
Kudo, Nobuki [3 ]
Kubota, Yoshinobu [4 ]
Terasaka, Shunsuke [1 ]
Houkin, Kiyohiro
机构
[1] Hokkaido Univ, Dept Neurosurg, Grad Sch Med, Kita Ku, Sapporo, Hokkaido 0608638, Japan
[2] TOTO Ltd, Res Inst, Biotechnol Grp, Kitakyushu, Fukuoka 8028601, Japan
[3] Hokkaido Univ, Grad Sch Informat Sci & Technol, Lab Biol Engn, Sapporo, Hokkaido 0600814, Japan
[4] Yokohama City Univ, Dept Urol, Grad Sch Med, Yokohama, Kanagawa 2360004, Japan
关键词
Glioma; Fluorescence assay; Photodynamic therapy; Polyethylene glycol; Sonodynamic therapy; Water-dispersed titanium dioxide; ADMINISTERED TITANIUM-DIOXIDE; GUIDED FOCUSED ULTRASOUND; 5-AMINOLEVULINIC ACID; CANCER-CELLS; IN-VITRO; BRAIN; TIO2; HEMATOPORPHYRIN; NANOPARTICLES; APOPTOSIS;
D O I
10.1016/j.ultsonch.2010.12.017
中图分类号
O42 [声学];
学科分类号
070206 ; 082403 ;
摘要
Sonodynamic therapy is expected to be a novel therapeutic strategy for malignant gliomas. The titanium dioxide (TiO2) nanoparticle, a photosensitizer, can be activated by ultrasound. In this study, by using water-dispersed TiO2 nanoparticles, an in vitro comparison was made between the photodynamic and sonodynamic damages on U251 human glioblastoma cell lines. Water-dispersed TiO2 nanoparticles were constructed by the adsorption of chemically modified polyethylene glycole (PEG) on the TiO2 surface (TiO2/PEG). To evaluate cytotoxicity, U251 monolayer cells were incubated in culture medium including 100 mu g/ml of TiO2/PEG for 3 h and subsequently irradiated by ultraviolet light (5.0 mW/cm(2)) or 1.0 MHz ultrasound (1.0 W/cm(2)). Cell survival was estimated by MTT assay 24 h after irradiation. In the presence of TiO2/PEG, the photodynamic cytotoxic effect was not observed after 20 min of an ultraviolet light exposure, while the sonodynamic cytotoxicity effect was almost proportional to the time of sonication. In addition, photodynamic cytotoxicity of TiO2/PEG was almost completely inhibited by radical scavenger, while suppression of the sonodynamic cytotoxic effect was not significant. Results of various fluorescent stains showed that ultrasound-treated cells lost their viability immediately after irradiation, and cell membranes were especially damaged in comparison with ultraviolet-treated cells. These findings showed a potential application of TiO2/PEG to sonodynamic therapy as a new treatment of malignant gliomas and suggested that the mechanism of TiO2/PEG mediated sonodynamic cytotoxicity differs from that of photodynamic cytotoxicity. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:1197 / 1204
页数:8
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