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KAKEN_23590054seika.pdf
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Title |
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リガンドの新規修飾方法によるがんターゲティングナノ製剤の開発
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リガンド ノ シンキ シュウショク ホウホウ ニ ヨル ガン ターゲティング ナノ セイザイ ノ カイハツ
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Rigando no shinki shushoku hoho ni yoru gan tagetingu nano seizai no kaihatsu
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Development of targeting liposomal drugs using functional coating a folate-polymer conjugate
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米谷, 芳枝
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マイタニ, ヨシエ
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Maitani, Yoshie
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慶應義塾大学・薬学部・研究員
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Research team head
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科研費研究者番号 : 10231581
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2014
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科学研究費補助金研究成果報告書
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2013
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リポソームとリガンド高分子との新規な修飾方法を確立して、がんターゲティングナノ粒子製剤を開発した。Layer-by-layer(LBL)法を応用して、葉酸結合率の異なる2種類の葉酸結合ポリ-L-リシンを合成して、負電荷のドキソルビシン封入リポソームに静電的に被覆した。この製剤は葉酸受容体高発現KB細胞に対して選択的な取り込みと細胞毒性を示した。また、従来の葉酸PEG修飾リポソームとは異なり、葉酸修飾率の高い高分子被覆リポソームのほうが、低い修飾率のものよりKB細胞に取り込まれ、修飾方法によって葉酸の表面分布状態が異なることが推察された。
The tumor targeting of anticancer drugs is important in chemotherapy to reduce serious side-effect for patients. Folate-polymer-coated liposomes were developed for targeted chemotherapy using doxorubicin (DXR) as a model drug. Folate-poly(L-lysine) (F-PLL) conjugates were synthesized. DXR-loaded anionic liposomes were coated with F-PLL, using Layer-by layer method. In KB cells overexpressing folate receptors, F-PLL-coated liposomal DXR increased the cellular association and cytotoxicity compared with that of PLL-coated liposomes. Differently in folate-PEG modified liposome, higher folate conjugated PLL-coated liposome showed higher KB cellular uptake, suggesting different distribution of folate at the surface of liposomes.
Folate-targeted liposomes were prepared successfully by coating the folate-polymer-conjugate F-PLL.
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研究種目 : 基盤研究(C)
研究期間 : 2011~2013
課題番号 : 23590054
研究分野 : 医歯薬学
科研費の分科・細目 : 薬学・物理系薬学
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