Prevention of pulmonary metastasis from subcutaneous tumors by binary system-based sustained delivery of catalase

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• 作者：Kenji Hyoudou ; Makiya Nishikawa ; Mai Ikemura ; Yuki Kobayashi ; Adam Mendelsohn ; Nobuhiko Miyazaki ; Yasuhiko Tabata ; Fumiyoshi Yamashita ; Mitsuru Hashida
• 关键词：Catalase ; Pegylation ; Gelatin hydrogel ; Controlled release ; Spontaneous metastasis
• 刊名：Journal of Controlled Release
• 出版年：2009
• 出版时间：20 July 2009
• 年：2009
• 卷：137
• 期：2
• 页码：110-115
• 全文大小：274 K

文摘

Catalase delivery can be effective in inhibiting reactive oxygen species (ROS)-mediated acceleration of tumor metastasis. Our previous studies have demonstrated that increasing the plasma half-life of catalase by pegylation (PEG-catalase) significantly increases its potency of inhibiting experimental pulmonary metastasis in mice. In the present study, a biodegradable gelatin hydrogel formulation was used to further increase the circulation time of PEG-catalase. Implantation of ¹¹¹In-PEG-catalase/hydrogel into subcutaneous tissues maintained the radioactivity in plasma for more than 14 days. Then, the effect of the PEG-catalase/hydrogel on spontaneous pulmonary metastasis of tumor cells was evaluated in mice with subcutaneous tumor of B16-BL6/Luc cells, a murine melanoma cell line stably expressing luciferase. Measuring luciferase activity in the lung revealed that the PEG-catalase/hydrogel significantly (P < 0.05) inhibited the pulmonary metastasis compared with PEG-catalase solution. These findings indicate that sustaining catalase activity in the blood circulation achieved by the use of pegylation and gelatin hydrogel can reduce the incidence of tumor cell metastasis.