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Increased antitumor effect of chemotherapy, using radiosensitive microcapsules containing anti-RLIP076

anti-RLIP076含有放射線感受性のマイクロカプセルを使用する化学療法の抗腫瘍効果の増加

原田 聡*; 江原 茂*; 石井 慶造*; 佐藤 隆博; 山崎 浩道*; 松山 成男*; 神谷 富裕

Harada, Satoshi*; Ehara, Shigeru*; Ishii, Keizo*; Sato, Takahiro; Yamazaki, Hiromichi*; Matsuyama, Shigeo*; Kamiya, Tomihiro

RLIP 76 is a peptide (76 kDa) that is activated by radiation, which mediates ATP-dependent primary active efflux of organic anionic compounds (reactive oxygen species, ROS), and cationic chemotherapeutic drugs (doxorubicin, adriacin, carboplatin). Thus, the inhibition of RLIP76 by anti-RLIP 76 antibody might inhibit the efflux of ROS and chemotherapeutic reagents, and increase intratumoral concentration of chemotherapeutic reagents, which might result in increased antitumor effect. In this study, we encapsulated carboplatin (platinum based anticancer drug) and anti-RLIP 76 IgG, and their antitumor effect was tested in combination with radiation. In micro-PIXE camera imaging, unirradiated microcapsules had smooth surface and distinct liquid core. After radiation, the contour of microcapsules were made irregular and releasing of carboplatin could be observed. Then anti-RLIP-76 IgG inhibited the efflux of carboplatin from tumors.

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