软磷脂修饰纳米颗粒与仿生磷脂膜之间相互作用的机理探索

项目名称： 软磷脂修饰纳米颗粒与仿生磷脂膜之间相互作用的机理探索

项目编号： No.21264016

项目类型： 地区科学基金项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 蒋中英

作者单位： 伊犁师范学院

项目金额： 52万元

中文摘要： 纳米颗粒的内吞机理和毒性成因已成为药物输运中研究的热点问题。纳米颗粒外层包裹磷脂膜后，提高了纳米颗粒的生物相容性。我们选择"磷脂膜包裹的纳米颗粒"作为纳米颗粒模型，研究膜与膜之间的相互作用，尝试1）用盐调控双性离子型磷脂包裹的纳米颗粒与支撑膜融合发生的概率；2）通过改变磷脂的链长度和链中双键的个数来改变膜的流动性，调整融合的时间进程；3)改变修饰膜的带电量和电荷分布来改变融合速率4）改变纳米颗粒仿生膜与纳米颗粒的粘滞力来调整内外层之间的耦合作用，调整膜的融合方式。基于仿生支撑膜和巨囊泡体系，利用荧光显微镜和电化学方法，从不同尺度观测仿生纳米颗粒膜与仿生膜的融合中间态及其动力学过程，探索fusion的可控机理。而该课题的开展和完成，将为最小化仿生纳米颗粒的生物毒性、控制纳米颗粒在不同种类细胞中的内吞方式和吞噬速率，优化仿生膜修饰胶体的载药效率提供有价值的参考。

中文关键词： 膜融合；纳米颗粒；磷脂转移；半融合；两亲性磷脂分子

英文摘要： TThe endocytosis mechanism and toxicity origin of nanoparticles have attracted great attention in resent drug delivery research. The nanoparticle biocompatibility can be improved significantly by phospholipid membrane encapsulation. We choose the membrane-coated nanoparticle as the particle model to explore the intermembrane interaction mechanism, trying to solve the following scientific questions. 1) Salt response of fusion probability between the coating membrane and supported lipid bilayer; 2) Using lipid alkyl chain length and the double bond number to regulate lipid lateral diffusion rate and fusion rate; 3) Using membrane charge density and charge distribution to regulate fusion dynamics; 4) Changing membrane adhesion energy to nanoparticle to adjust the coupling between the leaves and hence the membrane fusion pathway. Based on the supported lipid bilayer and giant lipid vesicle model membrane systems, combining fluorescence microscopy and electrochemistry characterization methods, the fusion intermediate and dynamics can be studied from different length scales. This research can provide valuable insights into the minimization strategy to reduce the biomimetic nanoparticle toxicity, the adjustable way to modify the nanoparticle endocytic pathway/rate, and optimization method to improve the drug delivery e

英文关键词： membrane fusion；nanoparticles；lipid exchange；hemifusion；amphiphilic lipid