Cytoplasmic delivery of liposomal contents mediated by an acid-labile cholesterol-vinyl ether-PEG conjugate.
Cytoplasmic delivery of liposomal contents mediated by an acid-labile cholesterol-vinyl ether-PEG conjugate.
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DOI：
10.1021/bc800239b
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发表时间：
2009-01
影响因子：
4.7
通讯作者：
Thompson, David H.
中科院分区：
文献类型：
--
作者：
Boomer, Jeremy A.;Qualls, Marquita M.;Inerowicz, H. Dorota;Haynes, Robert H.;Patri, V. Srilakshmi;Kim, Jong-Mok;Thompson, David H.
一种可酸裂解的 PEG 脂质 1′-(4′-胆固醇氧基-3′-丁烯基)-ω-甲氧基-聚乙烯[112]乙醇酸酯 (CVEP) 已开发出来，当作为次要成分 (0.5–5 mol%) 分散在 1,2-二油酰-sn-甘油-3-磷酸乙醇胺中时，可产生稳定的脂质体 （涂料）。弱酸性 pH 条件下 CVEP 的裂解导致潜在融合 DOPE 脂质体的去聚乙二醇化，从而引发内容物释放。本文描述了从容易获得的前体 1,4-丁二醇、胆固醇和 mPEG 酸开始，通过六步顺序合成 CVEP。还报道了 CVEP:DOPE 脂质体分散体的水解速率和释放动力学作为 CVEP 负载量的函数，以及 9:91 CVEP:DOPE 混合物的低温透射电子显微镜和 pH 依赖性单层特性。当叶酸受体阳性 KB 细胞暴露于含有 0.1 mol% 叶酸修饰的 1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-聚乙烯[76] 乙醇酰胺（叶酸-PEG-DSPE）的负载钙黄绿素的 5:95 CVEP:DOPE 脂质体（叶酸-PEG-DSPE）时，钙黄绿素有效递送至细胞的细胞质 通过荧光显微镜和流式细胞术进行观察。这些细胞中脂质混合的荧光共振能量转移分析与脂质体和内体膜之间的膜膜融合一致。
An acid-cleavable PEG lipid, 1′-(4′-cholesteryloxy-3′-butenyl)-ω-methoxy-polyethylene[112] glycolate (CVEP), has been developed that produces stable liposomes when dispersed as a minor component (0.5–5 mol%) in 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Cleavage of CVEP at mildly acidic pH’s results in dePEGylation of the latently fusogenic DOPE liposomes, thereby triggering the onset of contents release. This paper describes the synthesis of CVEP via a six step sequence starting from the readily available precursors 1,4-butanediol, cholesterol, and mPEG acid. The hydrolysis rates and release kinetics from CVEP:DOPE liposome dispersions as a function of CVEP loading, as well as the cryogenic transmission electron microscopy and pH-dependent monolayer properties of 9:91 CVEP:DOPE mixtures, also are reported. When folate-receptor positive KB cells were exposed to calcein-loaded 5:95 CVEP:DOPE liposomes containing 0.1 mol% folate-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-polyethylene[76] glycolamide (folate-PEG-DSPE), efficient delivery of the calcein cargo to the cytoplasm of the cells was observed as determined by fluorescence microscopy and flow cytometry. Fluorescence resonance energy transfer analysis of lipid mixing in these cells was consistent with membrane-membrane fusion between the liposome and endosomal membranes.
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影响因子：
3.4
作者：
Boomer, JA;Thompson, DH
通讯作者：
Thompson, DH
影响因子：
82.9
作者：
Alexandrakis, G;Brown, EB;Jain, RK
通讯作者：
Jain, RK
影响因子：
3.4
作者：
Auguste, DT;Prud'homme, RK;Kohn, J
通讯作者：
Kohn, J
DOI：
10.1016/0005-2736(91)90246-5
发表时间：
1991-07-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ALLEN, TM;HANSEN, C;YAUYOUNG, A
通讯作者：
YAUYOUNG, A
影响因子：
3.5
作者：
Chang, Yu-Cheng;Herath, Jayatilake;Chow, Christine S.
通讯作者：
Chow, Christine S.