脂质体在聚合物多层表面的吸附及支撑流动磷脂双层形成的机理研究

Lipid bilayer membrane is the most important and well-known self-assembled structure in nature. Until now, several membrane models including lipid monolayer, liposome, black lipid membrane, solid or polymer-supported lipid membrane have been developed in order to better understand the function of biomembranes. Among of them, solid-supported lipid membranes have attracted much attention due to their advantages like high stability, simple preparation and patterning, and compatibility with most of newly developed surface-sensitive facilities. Solid-supported lipid bilayer membranes are usually formed by vesicle fusion on a suitable substrate. Many studies have demonstrated the formation mechanism of liposomes containing simple lipid compositions fusing on a silicon dioxide substrate which includes five steps, i.e. liposome adsorption, deformation, fusion, rupture and formation of fluid lipid bilayer. However, when both lipid composition and surface property of solid supports are changed, the formation mechanism of supported lipid bilayer becomes very complex and more physiochemical parameters have to be taken into account. In this proposal, we will employ quartz crystal microbanlance, Kelvin force microscopy and dissipative particle dynamics method to study the adsorption of different liposomes on different polyelectrolyte multilayers, and then obtain the optimical parameters and mechanism of the controlled self-assemlby of polyelectrolyte multilayer-cushioned lipid bilayer. We hope our researches could clarify the misunderstanding upon the formation mechanism of polyelectrolyte multilayer-cushioned fluid lipid bilayer, i.e. the eletrostatic attaction between liposome and substrate could completely satisfy with the formation of polyelectrolyte multilayer-cushioned fluid lipid bilayer.

磷脂双层膜是自然界中最重要和最被人熟知的自组装结构之一。目前已发展了各种磷脂膜模型体系如单分子膜、脂质体、黑膜、固体或高分子支撑磷脂膜等来理解磷脂膜的性质和功能。其中，固体支撑磷脂膜拥有制备方法多样、稳定性高、易于阵列化、有利于各种表面敏感技术应用等优点，受到人们关注。它通常是由脂质体融合到合适的固体表面上形成的，大量的研究已阐明组成比较单一的脂质体在硅片表面的融合机理，即脂质体的吸附、变形、融合、破裂及支撑双层形成。然而当脂质体组分和固体支撑物的表面性质改变时，支撑双层形成的机理就比较复杂，需考虑更多物理化学因素的影响。本项目中，我们将利用石英晶体微天平、开尔文力显微镜技术及耗散粒子动力学模拟方法，研究脂质体在不同聚电解质多层表面的吸附，实现聚电解质多层支撑磷脂双层膜的可控自组装并阐明其形成机理，澄清当前文献报道中当脂质体与聚电解质多层在静电吸引的条件下即可形成流动支撑磷脂双层的误区。

磷脂双层膜是由两层具有两性的磷脂分子组成的薄膜，几乎所有细胞生物的细胞膜和许多病毒的包膜都主要有磷脂双分子层构成。尽管磷脂双层膜的种类繁多，人们更关注于不同维度的固体支撑磷脂膜形成机理及其广泛生物医学方向的应用。本项目中，我们集中研究了磷脂双层膜特别是源自THP-1免疫细胞磷脂膜碎片在聚电解质多层膜表面（微米粒子）可控组装并阐明其形成机理。并且通过实验进一步证明，这种基于聚电解质多层膜的阴阳型粒子对癌细胞具备靶向识别作用，且该靶向作用是源于THP-1免疫细胞膜碎片对粒子的伪装。基于此，我们又将该靶向识别阴阳离子体系应用于癌细胞的选择性识别并通过近红外激光完成药物的可控释放对癌细胞进行定向清除。在完成此部分实验之后，我们将磷脂双层膜吸附的基地的体系从2维基底扩展到2.5维的微纳米阵列聚电解质多层膜空腔再到3维微米粒子，基底的制备方法也从层层自组装的静电吸附扩展到了聚合物的一步浸渍提拉法再到聚电解质凝胶的电喷雾法，在不影响吸附膜功能的前提下，为药物输送体系提供了更多全新的概念和可靠地理论基础。