Lipids, curvature, and nano-medicine.
Lipids, curvature, and nano-medicine.
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DOI：
10.1002/ejlt.201100050
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发表时间：
2011-10
影响因子：
2.7
通讯作者：
Mouritsen, Ole G.
中科院分区：
文献类型：
--
作者：
Mouritsen, Ole G.
生物膜的层状脂质双层组分的物理性质由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的曲率应力不稳定性，其可以在局部或全局上在形态变化方面释放。特别是，不同脂质和蛋白质种类的平均分子形状以及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。不同的脂质，甾醇，和蛋白质对膜结构的影响进行了讨论，它示出了如何可以利用特定的分子剂，如脂肪酸，lysolipids，和其他两亲性溶质所带来的曲率应力调制，以构建智能药物递送系统的功能，通过曲率的酶促触发。实际应用：脂质分子形状的简单概念及其如何影响脂质聚集体的结构，特别是脂质双层和脂质体中的曲率和曲率应力，可以用于构建基于脂质体的药物递送系统，例如，用于癌症治疗的纳米药物。非层状形成的溶血脂和脂肪酸，其中一些可以被设计为前药，可以通过磷脂酶在患病组织中的作用产生，从而提供靶向药物释放和具有圆锥形形状的分子实体的增殖，其破坏靶细胞的渗透性屏障，因此可以增强功效。
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.
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