Carboxylated hyperbranched poly(glycidol)s for preparation of pH-sensitive liposomes
Carboxylated hyperbranched poly(glycidol)s for preparation of pH-sensitive liposomes
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DOI：
10.1016/j.jconrel.2010.03.001
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发表时间：
2011-01-05
影响因子：
10.8
通讯作者：
Kono, Kenji
中科院分区：
文献类型：
--
作者：
Yuba, Eiji;Harada, Atsushi;Kono, Kenji
作者先前的报告描述了使用用各种羧基化聚（缩水甘油）衍生物修饰的脂质体的细胞内递送。这些线性聚合物修饰的脂质体在细胞酸性区室中表现出pH依赖性的膜融合行为。然而，骨架结构对膜融合活性的影响仍然未知。因此，本研究专门研究了主链结构，以获得具有更高融合活性的pH敏感性聚合物，并揭示聚合物主链结构对与膜相互作用的影响。超支化聚缩水甘油（HPG）衍生物是一种新型的pH敏感性聚合物，可用于脂质体的修饰。所得的HPG衍生物表现出高的疏水性和强烈的相互作用与膜伴随着增加的聚合度（DP）。此外，HPG衍生物显示出比线性聚合物显示出更强的与膜的相互作用。用高DP的HPG衍生物修饰的脂质体将内容物递送到DC 2.4细胞（树突状细胞系）的胞质溶胶中，比线性聚合物修饰的脂质体更有效。结果表明，pH敏感聚合物的骨架结构影响其pH敏感性和与脂质体和细胞膜的相互作用。(C)2010爱思唯尔有限公司版权所有。
Previous reports by the authors described intracellular delivery using liposomes modified with various carboxylated poly(glycidol) derivatives. These linear polymer-modified liposomes exhibited a pH-dependent membrane fusion behavior in cellular acidic compartments. However, the effect of the backbone structure on membrane fusion activity remains unknown. Therefore, this study specifically investigated the backbone structure to obtain pH-sensitive polymers with much higher fusogenic activity and to reveal the effect of the polymer backbone structure on the interaction with the membrane. Hyperbranched poly(glycidol) (HPG) derivatives were prepared as a new type of pH-sensitive polymer and used for the modification of liposomes. The resultant HPG derivatives exhibited high hydrophobicity and intensive interaction with the membrane concomitantly with the increasing degree of polymerization (DP). Furthermore, HPG derivatives showed a stronger interaction with the membrane than the linear polymers show. Liposomes modified with HPG derivatives of high DP delivered contents into the cytosol of DC2.4 cells, a dendritic cell line, more effectively than the linear polymer-modified liposomes do. Results show that the backbone structure of pH-sensitive polymers affected their pH-sensitivity and interaction with liposomal and cellular membranes. (C) 2010 Elsevier B.V. All rights reserved.