Liposomes with double-stranded DNA anchoring the bilayer to a hydrogel core.
Liposomes with double-stranded DNA anchoring the bilayer to a hydrogel core.
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DOI：
10.1021/bm401155a
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发表时间：
2013-10-14
影响因子：
6.2
通讯作者：
Malmstadt, Noah
中科院分区：
文献类型：
--
作者：
Dayani, Yasaman;Malmstadt, Noah
脂质体是重要的生物分子纳米结构，在实验室中处理膜相关分子，在临床中传递药物。除了在生物医学上的应用外，它们还被广泛用作生物物理研究中的模型细胞膜。在这里，我们提出了一种基于脂质体的模型膜，模拟了膜驻留分子对细胞骨架的附着。为了促进这种附着，我们开发了一种基于脂质的杂交纳米结构，其中脂质体双层膜使用短双链DNA （dsDNA）连接物共价锚定在生物相容性聚乙二醇（PEG）水凝胶核上。双链dna连接体将存在于双分子层中的胆固醇基团与交联水凝胶主链中的乙烯基连接起来。完整的和表面活性剂处理的纳米颗粒的尺寸排除色谱（SEC）证实了锚定水凝胶结构的形成。透射电子显微镜（TEM）显示，即使在去除未固定的磷脂后，仍有~100 nm的纳米颗粒。dsDNA基团在水凝胶-双分子层界面的位置用荧光测定法确认。使用DNA作为双分子层和水凝胶核心之间的连接物，可以根据温度释放锚定相互作用，产生具有可寻址杂交位点的聚合物纳米凝胶，并为潜在的未来寡核苷酸药物递送应用提供原型结构。
Liposomes are important biomolecular nanostructures for handling membrane-associated molecules in the lab and delivering drugs in the clinic. In addition to their biomedical applications, they have been widely used as model cell membranes in biophysical studies. Here we present a liposome-based model membrane that mimics the attachment of membrane-resident molecules to the cytoskeleton. To facilitate this attachment, we have developed a lipid-based hybrid nanostructure in which the liposome bilayer membrane is covalently anchored to a biocompatible poly(ethylene) glycol (PEG) hydrogel core using short double-stranded DNA (dsDNA) linkers. The dsDNA linkers connect cholesterol groups that reside in the bilayer to vinyl groups that are incorporated in the cross-linked hydrogel backbone. Size exclusion chromatography (SEC) of intact and surfactant-treated nanoparticles confirms the formation of anchored hydrogel structures. Transmission electron microscopy (TEM) shows ~100 nm nanoparticles even after removal of unanchored phospholipids. The location of dsDNA groups at the hydrogel-bilayer interface is confirmed with a fluorescence assay. Using DNA as a linker between the bilayer and a hydrogel core allows for temperature-dependent release of the anchoring interaction, produces polymer nanogels with addressible hybridization sites on their surface, and provides a prototype structure for potential future oligonucleotide drug delivery applications.
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