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

我们最近发现磷脂和胆固醇核苷缀合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。该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质分子的多功能储存库。为此，我们将研究这些核脂基管的物理化学性质，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。新的核脂偶联物的合理设计将使我们能够探索不同官能团的具体贡献，并分析决定管结构的分子间相互作用。结合生物物理方法，我们将在不同的实验条件下研究试管的组成、形态和稳定性。这种方法将为开发“可调”系统提供必要的洞察力，该系统可以定制以显示特征属性。作为这条路线的第一步，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，我们将探索具有亲脂分子的管的表面功能化策略。最后，我们将评估它们在模型细胞培养系统中的生物相容性。

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.