Efficient intracellular drug and gene delivery using folate receptor-targeted pH-sensitive liposomes composed of cationic/anionic lipid combinations
Efficient intracellular drug and gene delivery using folate receptor-targeted pH-sensitive liposomes composed of cationic/anionic lipid combinations
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DOI：
10.1016/s0168-3659(02)00017-2
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发表时间：
2002-04-23
影响因子：
10.8
通讯作者：
Lee, RJ
中科院分区：
文献类型：
--
作者：
Shi, GF;Guo, WJ;Lee, RJ
pH敏感的脂质体的目的是促进有效释放的截留剂在响应低pH值。在这项研究中，新型的pH敏感的脂质体组成的阳离子/阴离子脂质组合的细胞内药物和基因传递进行了评估。第一种是卵磷脂组成的脂质体。二甲基二辛基溴化铵（DDAB）、胆固醇半琥珀酸酯（CHEMS）和吐温-80（25：25：49：1，mol/mol）在pH 7.4下稳定地包封钙黄绿素，并在酸性pH下经历快速内容物释放和不可逆聚集。与掺入二油酰磷脂酰乙醇胺的pH敏感性脂质体相比，这些脂质体在血清存在下显示出改善的pH敏感性保留。叶酸受体（FR）在多种人类肿瘤中扩增，可通过将0.1 mol%叶酸-聚乙二醇-磷脂酰乙醇胺（f-PEG-PE）掺入脂质体中来靶向。已显示f-PEG-PE促进FR介导的脂质体内吞到KB人口腔癌细胞中，所述KB人口腔癌细胞表达扩增的FR。FR靶向的pH敏感性脂质体产生截留的钙黄绿素的增加的胞质释放。如荧光显微镜所示，并且包埋的胞嘧啶-β-D-阿拉伯呋喃糖苷的细胞毒性增强。如KB细胞中IC 50降低11倍所示。与FR靶向非pH敏感性脂质体相比。此外，FR靶向pH敏感脂质体由DDAB/CHEMS/f-PEG-PE组成。与聚赖氨酸浓缩的质粒DNA组合，显示在10%血清存在下介导FR特异性递送荧光素酶报告基因进入KB细胞。这些发现表明，阳离子脂质含有pH敏感的脂质体，结合FR靶向，是细胞内药物和基因递送的有效载体。(C)2002 Elsevier Science B. V.保留所有权利。
pH-sensitive liposomes are designed to promote efficient release of entrapped agents in response to low pH. In this study, novel pH-sensitive liposomes consisting of cationic/anionic lipid combinations are evaluated for intracellular drug and gene delivery. First, liposomes composed of egg phosphatidylcholine. dimethldioctacylammonium bromide (DDAB), cholesteryl hemisuccinate (CHEMS), and Tween-80 (25:25:49:1, mol/mol) were shown to stably entrap calcein at pH 7.4 and undergo rapid content release and irreversible aggregation under acidic pH. Compared to pH-sensitive liposomes incorporating dioleoylphosphatidylethanolamine, these liposomes showed improved retention of pH-sensitivity in the presence of serum. The folate receptor (FR), which is amplified in a wide variety of human tumors, could be targeted by incorporating 0.1 mol% folate-polyethyleneglycol-phosphatidylethanolamine (f-PEG-PE) into liposomes. f-PEG-PE has been shown to facilitate FR-mediated endocytosis of liposomes into KB human oral cancer cells, which express amplified FR. FR-targeted pH-sensitive liposomes produced increased cytosolic release of entrapped calcein. as shown by fluorescence microscopy, and enhanced cytotoxicity of entrapped cytosine-beta-D-arabinofuranoside. as shown by an 11-fold reduction in the IC50 in KB cells. compared to FR-targeted non-pH-sensitive liposomes. Furthermore, FR-targeted pH-sensitive liposomes composed of DDAB/CHEMS/f-PEG-PE. combined with polylysine-condensed plasmid DNA, were shown to mediate FR-specific delivery of a luciferase reporter gene into KB cells in the presence of 10% serum. These findings suggest that cationic lipid-containing pH-sensitive liposomes, combined with FR targeting, are effective vehicles for intracellular drug and gene delivery. (C) 2002 Elsevier Science B.V. All rights reserved.