Transferrin-Modified Liposomes Equipped with a pH-Sensitive Fusogenic Peptide: An Artificial Viral-like Delivery System

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• 作者：Tomoyuki Kakudo ; Shinji Chaki ; Shiroh Futaki ; Ikuhiko Nakase ; Kenichi Akaji ; Toru Kawakami ; Kazuo Maruyama ; Hiroyuki Kamiya ; and Hideyoshi Harashima
• 刊名：Biochemistry
• 出版年：2004
• 出版时间：May 18, 2004
• 年：2004
• 卷：43
• 期：19
• 页码：5618 - 5628
• 全文大小：749K
• 年卷期：v.43,no.19(May 18, 2004)
• ISSN：1520-4995

文摘

Liposomes are one of the most promising systems for selective cellular targeting via introductionof specific ligands for cell-surface receptors. After being taken up by the cells, these liposomes usuallyfollow intracellular pathways of receptor-mediated endocytosis. Control of intracelluar trafficking is requiredfor optimized drug delivery. In this study, we elucidated the intracellular fate of transferrin-modifiedliposomes and succeeded in altering it by introducing the pH-sensitive fusogenic peptide, GALA(WEAALAEALAEALAEHLAEALAEALEALAA). Transferrins that are chemically attached to aliposomal surface (Tf-L) were internalized via receptor-mediated endocytosis more slowly than unmodifiedtransferrins. In contrast to the recyclable nature of transferrin, liposome-attached transferrins togetherwith encapsulated rhodamines were retained in vesicular compartments. When GALA was introducedinto liposomal membranes using a cholesteryl moiety for anchoring (Chol-GALA), rhodamines wereefficiently released and diffused into the cytosol. The addition of GALA to the Tf-L-containing mediumor the encapsulation of GALA in Tf-L did not induce similar effects. These results clearly indicate thatGALA must be present on the surface of liposomes to exert its function. In vitro energy transfer anddynamic light scattering experiments suggested that the endosomal escape of the encapsulates in Tf-Lequipped with Chol-GALA can be attributed to pH-dependent membrane fusion. With GALA present onthe surface, intracellular trafficking of liposomes after receptor-mediated endocytosis could be successfullycontrolled.