Department of Chemical and Biological Engineering, University of Colorado, 3415 Colorado Avenue, JSC Biotech Building, Boulder, Colorado 80303, USA.
Soft Matter. 2018 Sep 26;14(37):7645-7652. doi: 10.1039/c8sm01329b.
Synthetic unilamellar liposomes, functionalized to enable novel characteristics and behavior, are of great utility to fields such as drug delivery and artificial cell membranes. However, the generation of these liposomes is frequently highly labor-intensive and time consuming whereas in situ liposome formation presents a potential solution to this problem. A novel method for in situ lipid formation is developed here through the covalent addition of a thiol-functionalized lysolipid to an acrylate-functionalized tail via the thiol-Michael addition reaction with potential for inclusion of additional functionality via the tail. Dilute, stoichiometric mixtures of a thiol lysolipid and an acrylate tail reacted in an aqueous media at ambient conditions for 48 hours reached nearly 90% conversion, forming the desired thioether-containing phospholipid product. These lipids assemble into a high density of liposomes with sizes ranging from 20 nm to several microns in diameter and include various structures ranging from spheres to tubular vesicles with structure and lamellarity dependent upon the catalyst concentration used. To demonstrate lipid functionalization, an acrylate tail possessing a terminal alkyne was coupled into the lipid structure. These functionalized liposomes enable photo-induced polymerization of the terminal alkyne upon irradiation.
合成的单层脂质体经过功能化处理，使其具有新的特性和行为，在药物输送和人工细胞膜等领域具有很大的用途。然而，这些脂质体的产生通常非常耗费人力和时间，而原位脂质体形成则为解决这个问题提供了一种潜在的解决方案。本文提出了一种通过硫醇功能化赖氨酸脂质与丙烯酰基化尾通过硫醇-Michael 加成反应共价连接，从而原位形成脂质的新方法，通过尾端有可能引入额外的功能。在环境条件下，将硫醇赖氨酸脂质和丙烯酰基尾的稀、化学计量混合物在水性介质中反应 48 小时，达到近 90%的转化率，形成所需的含硫醚的磷脂产物。这些脂质组装成高密度的脂质体，直径从 20nm 到几微米不等，包括各种结构，从球体到管状囊泡，结构和层状结构取决于所用催化剂的浓度。为了证明脂质的功能化，将末端炔烃的丙烯酰基尾偶联到脂质结构中。这些功能化的脂质体能够在照射时引发末端炔烃的光诱导聚合。
