Effect of Protein-Encapsulation on Thermal Structural Stability of Liposome Composed of Glycosphingolipid/Cholesterol/Phospholipid
Effect of Protein-Encapsulation on Thermal Structural Stability of Liposome Composed of Glycosphingolipid/Cholesterol/Phospholipid
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DOI：
10.1021/jp511534u
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发表时间：
2015-02-26
影响因子：
3.3
通讯作者：
Shimizu, Nobutaka
中科院分区：
文献类型：
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作者：
Hirai, Mitsuhiro;Sato, Shoki;Shimizu, Nobutaka
我们利用同步辐射小角和广角X射线散射（SR-SWAXS）研究了包封蛋白质的脂质体的热结构稳定性。脂质体由于其生物降解性和生物相容性而被认为是有效的药物递送系统（DDS），因为它们可以降低药物毒性，并且可以提供各种类型药物的有希望的载体。然而，尽管对脂质体进行了大量的研究，但很少了解脂质体包封蛋白质的物理化学特性。所研究的脂质体的特征在于脂质组成（酸性鞘糖脂（神经节苷脂）/胆固醇/磷脂的混合物）。神经节苷脂是脂筏的主要成分之一，在细胞信号传导中起着平台作用。我们已经发现，蛋白质的包封提高了脂质体膜的热转变温度，并抑制其形状的变形。这些结果表明，不仅膜蛋白，而且水溶性蛋白也通过渗透压和膜弹性之间的相互作用影响脂质体的稳定性。此外，我们还发现了依赖于脂质体中神经节苷脂的摩尔含量的尺寸效应的存在，表明神经节苷脂分子控制脂质体的尺寸和有效表面电荷的能力。从两个不同的观点来看，目前的结果具有重要意义。一个是蛋白质在有限空间（如细胞）内的限制效应，另一个是使用神经节苷脂的新型DDS的稳定性。由于神经节苷脂固有的特性，其有望成为具有靶向和长循环特性的脂质体DDS。
We have studied the thermal structural stability of liposomes encapsulating proteins by using synchrotron radiation small- and wide-angle X-ray scattering (SR-SWAXS). Liposomes are known to be effective drug-delivery systems (DDSs) because they can reduce drug toxicity due to biodegradability and biocompatibility and can offer promising carriers of various types of drugs. However, in spite of numerous studies of liposomes, physicochemical characteristics of liposomes entrapping proteins are rarely known. The liposome studied is characterized by the lipid composition (mixture of acidic glycosphingolipid (ganglioside)/cholesterol/phospholipid). Gangliosides are one of the major constituents of so-called lipid rafts playing the role of a platform of cell-signaling. We have found that the encapsulation of proteins elevates the thermal transition temperature of the liposome membrane and suppresses the deformation of its shape. The present results suggest that not only membrane proteins, but also water-soluble proteins affect liposome stability through the revalence between osmotic pressure and membrane elasticity. In addition, we have found the presence of the size-effect depending on the molar content of gangliosides in the liposome, indicating the ability of ganglioside molecule controlling both the size and effective surface charge of the liposome. The present results would have significance from two different points of view. One is the confinement effect of proteins within a limited space like cell, and the other is a stability of a new type of DDS using gangliosides. Due to the intrinsic properties, gangliosides are expected to be promising agents for targeting and long-circulation properties of liposomal DDSs.