pHLIP®介导的 PEGylated 脂质体递送至癌细胞。
pHLIP®-mediated delivery of PEGylated liposomes to cancer cells.
机构信息
Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI 02881, USA.
出版信息
J Control Release. 2013 May 10;167(3):228-37. doi: 10.1016/j.jconrel.2013.01.037. Epub 2013 Feb 15.
Abstract
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.
摘要
我们开发了一种利用 pHLIP®（pH 低插入肽）使脂质体与细胞膜之间发生 pH 依赖性融合的方法，pHLIP® 仅在低 pH 值时插入细胞膜的脂质双层中。此前，我们已经确定了该肽的作用机制，并表明 pHLIP 可以靶向酸性病变组织。在这里，我们研究了 pHLIP 对 PEG 化脂质体的涂层如何影响细胞对脂质体的摄取。带正电荷的 PEG 化脂质体表面的 pHLIP 增强了膜融合和 pH 依赖性的脂质交换，从而增加了细胞摄取和有效载荷释放，并抑制了含有神经酰胺的脂质体对细胞的增殖作用。我们开发了一种新型的 pH 敏感型“融合性”pHLIP 脂质体，可用于将各种诊断和治疗药物选择性递送至酸性病变细胞。
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