pHLIP®-mediated delivery of PEGylated liposomes to cancer cells.

pHLIP®-mediated delivery of PEGylated liposomes to cancer cells.
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DOI:
10.1016/j.jconrel.2013.01.037
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发表时间:
2013-05-10
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Reshetnyak YK
Reshetnyak YK
中科院分区:
其他
文献类型:
--
作者:
Yao L;Daniels J;Wijesinghe D;Andreev OA;Reshetnyak YK

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我们开发了一种使用 pHLIP®(pH 低插入肽)实现脂质体与细胞膜之间 pH 依赖性融合的方法,该肽仅在低 pH 下插入膜的脂质双层中。之前我们建立了肽作用的分子机制,并表明 pHLIP 可以靶向酸性病变组织。在这里,我们研究了用 pHLIP 包被聚乙二醇化脂质体如何影响细胞对脂质体的摄取。聚乙二醇化脂质体表面上 pHLIP 的存在以 pH 依赖性方式增强了膜融合和脂质交换,导致细胞摄取和有效负载释放增加,并通过含有神经酰胺的脂质体抑制细胞增殖。开发了一种新型 pH 敏感、“融合”pHLIP 脂质体,可用于选择性地将各种诊断和治疗剂递送至酸性病变细胞。
We develop a method for pH-dependent fusion between liposomes and cellular membranes using pHLIP® (pH Low Insertion Peptide), which inserts into lipid bilayer of membrane only at low pH. Previously we establish the molecular mechanism of peptide action and show that pHLIP can target acidic diseased tissue. Here we investigate how coating of PEGylated liposomes with pHLIP might affect liposomal uptake by cells. The presence of pHLIP on the surface of PEGylated-liposomes enhanced membrane fusion and lipid exchange in a pH dependent fashion, leading to increase of cellular uptake and payload release, and inhibition of cell proliferation by liposomes containing ceramide. A novel type of pH-sensitive, “fusogenic” pHLIP-liposomes was developed, which could be used to selectively deliver various diagnostic and therapeutic agents to acidic diseased cells.
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