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Lipids, curvature, and nano-medicine
European Journal of Lipid Science and Technology ( IF 2.7 ) Pub Date : 2011-08-17 , DOI: 10.1002/ejlt.201100050
Ole G Mouritsen 1
Affiliation  

The physical properties of the lamellar lipid-bilayer component of biological membranes are controlled by a host of thermodynamic forces leading to overall tensionless bilayers with a conspicuous lateral pressure profile and build-in curvature-stress instabilities that may be released locally or globally in terms of morphological changes. In particular, the average molecular shape and the propensity of the different lipid and protein species for forming non-lamellar and curved structures are a source of structural transitions and control of biological function. The effects of different lipids, sterols, and proteins on membrane structure are discussed and it is shown how one can take advantage of the curvature-stress modulations brought about by specific molecular agents, such as fatty acids, lysolipids, and other amphiphilic solutes, to construct intelligent drug-delivery systems that function by enzymatic triggering via curvature. Practical applications: The simple concept of lipid molecular shape and how it impacts on the structure of lipid aggregates, in particular the curvature and curvature stress in lipid bilayers and liposomes, can be exploited to construct liposome-based drug-delivery systems, e.g., for use as nano-medicine in cancer therapy. Non-lamellar-forming lysolipids and fatty acids, some of which may be designed to be prodrugs, can be created by phospholipase action in diseased tissues thereby providing for targeted drug release and proliferation of molecular entities with conical shape that break down the permeability barrier of the target cells and may hence enhance efficacy.

中文翻译:

脂质、曲率和纳米医学

生物膜的层状脂质双层组分的物理性质受一系列热力学力控制,导致整体无张力双层具有明显的侧向压力分布和内置曲率 - 应力不稳定性,可以局部或全局释放形态变化。特别是,不同脂质和蛋白质种类的平均分子形状和形成非层状和弯曲结构的倾向是结构转变和生物功能控制的来源。讨论了不同脂质、甾醇和蛋白质对膜结构的影响,并展示了如何利用特定分子试剂(如脂肪酸、溶血脂和其他两亲性溶质)带来的曲率-应力调制,构建通过曲率酶促触发起作用的智能给药系统。实际应用:脂质分子形状的简单概念及其对脂质聚集体结构的影响,特别是脂质双层和脂质体中的曲率和曲率应力,可用于构建基于脂质体的药物输送系统,例如,在癌症治疗中用作纳米药物。非层状溶血脂和脂肪酸,其中一些可能被设计为前药,可以通过患病组织中的磷脂酶作用产生,从而提供靶向药物释放和圆锥形分子实体的增殖,破坏渗透性屏障靶细胞,因此可以提高疗效。实际应用:脂质分子形状的简单概念及其对脂质聚集体结构的影响,特别是脂质双层和脂质体中的曲率和曲率应力,可用于构建基于脂质体的药物输送系统,例如,在癌症治疗中用作纳米药物。非层状溶血脂和脂肪酸,其中一些可能被设计为前药,可以通过患病组织中的磷脂酶作用产生,从而提供靶向药物释放和圆锥形分子实体的增殖,破坏渗透性屏障靶细胞,因此可以提高疗效。实际应用:脂质分子形状的简单概念及其对脂质聚集体结构的影响,特别是脂质双层和脂质体中的曲率和曲率应力,可用于构建基于脂质体的药物输送系统,例如,在癌症治疗中用作纳米药物。非层状溶血脂和脂肪酸,其中一些可能被设计为前药,可以通过患病组织中的磷脂酶作用产生,从而提供靶向药物释放和圆锥形分子实体的增殖,破坏渗透性屏障靶细胞,从而提高疗效。特别是脂质双层和脂质体中的曲率和曲率应力,可用于构建基于脂质体的药物输送系统,例如用作癌症治疗中的纳米药物。非层状溶血脂和脂肪酸,其中一些可能被设计为前药,可以通过患病组织中的磷脂酶作用产生,从而提供靶向药物释放和圆锥形分子实体的增殖,破坏渗透性屏障靶细胞,因此可以提高疗效。特别是脂质双层和脂质体中的曲率和曲率应力,可用于构建基于脂质体的药物输送系统,例如用作癌症治疗中的纳米药物。非层状溶血脂和脂肪酸,其中一些可能被设计为前药,可以通过患病组织中的磷脂酶作用产生,从而提供靶向药物释放和锥形分子实体的增殖,这些分子实体打破了渗透性屏障靶细胞,因此可以提高疗效。
更新日期:2011-08-17
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