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外源性穿透肽修饰脂质诱导自发脂质体吸附。

Induction of Spontaneous Liposome Adsorption by Exogenous Surface Modification with Cell-Penetrating Peptide-Conjugated Lipids.

机构信息

Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, Saitama 337-8570, Japan.

出版信息

Langmuir. 2021 Aug 17;37(32):9711-9723. doi: 10.1021/acs.langmuir.1c01072. Epub 2021 Aug 3.

Abstract

The use of amphiphilic molecules such as poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) enables incorporation into liposome surfaces by exogenous addition as a result of the self-assembly with lipids. This technique can be applicable for manipulation of both liposomes and cells. In this study, we aimed to characterize Tat peptide (YGRKKRRQRRR)-conjugated PEG-lipids when used to exogenously surface modify liposomes (size: ca. 100 nm). We earlier reported that cells, which were surface modified with Tat peptides conjugated to PEG-lipids could attach spontaneously to material surfaces without any chemical modification. Here, we synthesized different types of Tat-PEG-lipids by combining PEG of different molecular weights (5 and 40 kDa) with different lipids with three acyl chains (myristoyl, palmitoyl, and stearoyl, respectively) and then studied the spontaneous adsorption of modified liposomes onto a substrate surface induced by the different Tat-PEG-lipids. The amount of adsorbed liposomes strongly depended on the number of incorporated Tat-PEG-lipid moieties: a decrease in both the PEG and the acyl chain lengths led to adsorption of higher amounts of liposomes. Furthermore, when a collagenase-cleavable amino acid sequence was inserted between the Tat sequence and the PEG segment, adsorbed liposomes could be harvested from the substrate by collagenase treatment with no difference in desorption efficiency between the different Tat-PEG-lipids. Thus, Tat-PEG-lipid can be a suitable tool for the manipulation of liposomes and cells.

摘要

使用两亲性分子,如聚乙二醇(PEG)-连接的磷脂(PEG-脂质),可以通过外源性添加来实现与脂质的自组装,从而将其整合到脂质体表面。这种技术可适用于脂质体和细胞的操作。在本研究中,我们旨在表征 Tat 肽(YGRKKRRQRRR)-连接的 PEG-脂质,当用于外源性表面修饰脂质体(大小:约 100nm)时。我们之前报道过,用连接到 PEG-脂质的 Tat 肽表面修饰的细胞可以自发地附着在材料表面,而无需任何化学修饰。在这里,我们通过将不同分子量(5 和 40 kDa)的 PEG 与具有三个酰基链(分别为豆蔻酰、棕榈酰和硬脂酰)的不同脂质相结合,合成了不同类型的 Tat-PEG-脂质,然后研究了不同 Tat-PEG-脂质诱导的修饰脂质体自发吸附到基底表面的情况。吸附的脂质体的量强烈依赖于结合的 Tat-PEG-脂质的数量:PEG 和酰基链长度的减少都会导致吸附更多的脂质体。此外,当在 Tat 序列和 PEG 段之间插入胶原酶可切割的氨基酸序列时,吸附的脂质体可以通过胶原酶处理从基底中回收,不同 Tat-PEG-脂质之间的解吸效率没有差异。因此,Tat-PEG-脂质可以成为操纵脂质体和细胞的合适工具。

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