Enhanced Gene Transfection in Macrophages by Histidine-Conjugated Mannosylated Cationic Liposomes
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概要
- 論文の詳細を見る
Targeted gene delivery to macrophages is important for the treatments of various immune diseases. Since macrophages express mannose receptors, development of efficient mannosylated non-viral carriers is an effective approach to macrophages-selective in vivo gene transfection. In this study, a pH-sensitive mannosylated cholesterol derivative, Man-His-C4-Chol, which possesses histidine (His) residues, containing lipoplexes (Man-His-lipoplexes) was characterized for transfection both in vitro and in vivo. In primary cultured macrophages, both Man-His-lipoplexes and mannosylated (Man)-lipoplexes showed significantly higher cellular uptake than bare-lipoplexes and there was no significant difference between Man-His-lipoplexes and Man-lipoplexes at 37 °C but the cellular uptake of these three lipoplexes was reduced at 4 °C. Similarly, the transfection efficacy of Man-His-lipoplexes showed significantly higher gene expression than bare-lipoplexes and Man-lipoplexes. After intraperitoneal administration to mice, Man-His-lipoplexes showed higher gene expression in peritoneally exuded cells (PECs) which contained macrophages than Man-lipoplexes and bare-lipoplexes at 3, 6, and 24 h. In addition, Man-His-lipoplexes showed higher gene expression than Gal-His-lipoplexes in PECs, suggesting that Man-His-lipoplexes are taken up by macrophages via mannose receptor-mediated endocytosis. These results suggest that Man-His-lipoplexes have superior transfection activity to Man-lipoplexes in macrophages.
- 日本薬学会の論文
著者
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Hashida Mitsuru
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Kawakami Shigeru
Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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Mukai Hidefumi
Department Of Molecular Engineering Graduate School Of Engineering Kyoto University
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HIGUCHI Yuriko
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Nakamura Kazumi
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Kuramoto Yukari
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Kawakami Shigeru
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Mukai Hidefumi
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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