Self-assembly of cholesterol-modified nucleosides into microtubes: Characterization, functionalization, loading and release of model substances

胆固醇修饰核苷自组装成微管：模型物质的表征、功能化、加载和释放

• 批准号: 195924843
• 负责人: Dr. Anna Arbuzova, since 1/2014
• 金额: --
• 依托单位: Institut für Chemie und Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/195924843?language=en
• 关键词: Self; assembly; cholesterol; modified; nucleosides

We have recently discovered that mixtures of phospholipid and a cholesteryl-nucleoside conjugate self-assemble into nano- and microtubes in aqueous solutions. The diameter of these tubes can be controlled depending upon preparation conditions. The goal of this project is to understand this selfassembly process and to utilize these structures as versatile reservoirs for drugs and mediator molecules. To this end, we will study the physico-chemical properties of these nucleolipid-based tubes, aiming to elucidate their mechanism of formation and the role of the multiple parameters that control the self-assembly. The rational design of new nucleolipid conjugates will allow us to probe the specific contributions of the different functional groups as well as to analyze the intermolecular interactions that determine the structure of the tubes. Using a combination of biophysical methods, we will study the composition, morphology, and stability of the tubes under varying experimental conditions. This approach will provide the necessary insight to develop a “tunable” system that can be tailored to display characteristic properties. As a first step in this line, we will test the capability of the nucleolipid tubes to act as reservoirs for model molecules, studying their entrapment and release. In addition, we will explore strategies for the surface functionalization of the tubes with lipophilic molecules. Finally, we will evaluate their biocompatibility in model cell culture systems.

我们最近发现，磷脂和胆固醇-核苷共轭物的混合物在水溶液中自组装成纳米管和微管。这些管的直径可以根据制备条件来控制。这个项目的目标是了解这种自组装过程，并利用这些结构作为药物和介体分子的通用水库。为此，我们将研究这些基于核脂质的管的物理化学性质，旨在阐明它们的形成机制和控制自组装的多个参数的作用。新的核脂质缀合物的合理设计将使我们能够探测不同官能团的具体贡献，以及分析决定管结构的分子间相互作用。使用生物物理方法的组合，我们将研究在不同的实验条件下的管的组成，形态和稳定性。这种方法将提供必要的洞察力，以开发一个“可调”的系统，可以定制显示特性。作为该系列的第一步，我们将测试核脂管作为模型分子储存库的能力，研究它们的捕获和释放。此外，我们将探索与亲脂性分子的管的表面功能化的策略。最后，我们将在模型细胞培养系统中评估其生物相容性。

项目成果

Micro- and nano-tubules built from loosely and tightly rolled up thin sheets.

• DOI: 10.1039/c5cp06084b
• 发表时间: 2016-01
• 期刊: Physical chemistry chemical physics : PCCP
• 作者: Luisa Losensky;Björn Goldenbogen;Gudrun Holland;M. Laue;Anca Petran;J. Liebscher;H. Scheidt;Alexander Vogel;D. Huster;E. Klipp;A. Arbuzova

Self-assembly of a cholesteryl-modified nucleoside into tubular structures from giant unilamellar vesicles

胆固醇修饰核苷从巨型单层囊泡自组装成管状结构

• DOI: 10.1039/c4ra11289j
• 发表时间: 2015
• 期刊: RSC Advances
• 影响因子: 3.9
• 作者: Losensky;Chiantia;Holland;Petran;Liebscher;Arbuzova
• 通讯作者: Arbuzova

DNA-controlled aggregation of virus like particles – mimicking a tetherin-like mechanism

• DOI: 10.1039/c4nj00724g
• 发表时间: 2014-10
• 期刊: New Journal of Chemistry
• 影响因子: 3.3
• 作者: D. Serien;C. Grimm;J. Liebscher;A. Herrmann;A. Arbuzova