Lateral phase separation in lipid-coated microbubbles
Lateral phase separation in lipid-coated microbubbles
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DOI：
10.1021/la052841v
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发表时间：
2006-04-25
期刊：
影响因子：
3.9
通讯作者：
Ferrara, KW
中科院分区：
文献类型：
--
作者：
Borden, MA;Martinez, GV;Ferrara, KW
在设计用于分子成像和靶向药物递送的脂质涂层微泡超声造影剂时，壳物质的表面分布是重要的，因为它决定了配体位置、刷覆盖率和载药量等性质。我们使用了光谱和显微镜技术相结合，以测试的主要磷脂酰胆碱（PC）和脂聚合物物种是完全混溶的单层壳内的流行观念。NMR光谱表明，壳组成大致相当于主体脂质比。FTIR光谱显示对应于主要PC物种的主要相变温度的尖锐熔融峰，从室温扫描时没有观察到预转变，表明单一的PC丰富的有序相。电子显微镜和荧光显微镜显示了一个不均匀的微观结构与黑暗（有序）域和明亮（无序）的地区。结构域的形成是向热的和可逆的。荧光标记的脂质聚合物壳形成后表明，它的分区优先进入无序的域间区域。因此，有序的域主要由PC组成，而无序的域间区域富含脂聚合物。在所有脂聚合物浓度（0.5至20摩尔%）下观察到相不均匀性，并且相分离的程度随脂聚合物含量增加。的组成和温度依赖性：的微观结构表明，相分离是驱动pherically，而不是一个动力学捕获的遗迹壳形成过程。微观结构的整体变化很大，包括异常三相共存的存在，突出了单层壳的非平衡（历史依赖）性质。
In the design of lipid-coated microbubble ultrasound contrast agents for molecular imaging and targeted drug delivery, the surface distribution of the shell species is important because it dictates such properties as ligand location, brush coverage, and amount of drug loading. We used a combination of spectroscopy and microscopy techniques to test the prevailing notion that the main phosphatidyl choline (PC) and lipopolymer species are completely miscible within the monolayer shell. NMR spectroscopy showed that the shell composition is roughly equivalent to the bulk lipid ratio. FTIR spectroscopy showed a sharp melting peak corresponding to the main phase-transition temperature of the main PC species, with no observed pretransitions while scanning from room temperature, indicating a single PC-rich ordered phase. Electron and fluorescence microscopy showed a heterogeneous microstructure with dark (ordered) domains and bright (disordered) regions. Domain formation was thermotropic and reversible. Fluorescent labeling of the lipopolymer following shell formation showed that it partitions preferentially into the disordered interdomain regions. The ordered domains, therefore, are composed primarily of PC, and the disordered interdomain regions are enriched in lipopolymer. Phase heterogeneity was observed at all lipopolymer concentrations (0.5 to 20 mol %), and the degree of phase separation increased with lipopolymer content. The composition and temperature dependence: of the microstructure indicates that phase separation is driven thermodynamically rather than being a kinetically trapped relic of the shell-formation process. The overall high variation in microstructure, including the existence of anomalous three-phase coexistence, highlights the nonequilibrium (history-dependent) nature of the monolayer shell.