Optimized the gene and drug delivery using liposomes based on the controlled liposomal surface property

虽然脂质体主要是药物和基因的载体，但为了临床应用各种类型的药物，开发新的有效的、细胞选择性的载体系统是必不可少的。在本研究中，我们对新型表面修饰脂质体进行了评价，目的是开发具有细胞选择性或与内源性成分相互作用可控的高级脂质体。在本研究中，我们合成了新的半乳糖化和甘露糖化胆固醇衍生物，分别用于肝实质细胞和非实质细胞的药物和基因传递。这些衍生物具有双重功能，即胆固醇用于固定脂质体表面的糖部分，糖残基用于细胞表面受体。体外实验表明，糖基化脂质体在受体介导的内吞作用中被有效吸收。经静脉给药后，糖基化脂质体被表达受体的细胞有效吸收。我们还制备了用于肝细胞选择性基因传递的糖基化阳离子脂质体/质粒DNA复合物。受体介导的基因传递系统能够将外源DNA引入体内的特定细胞类型。然而，我们已经证实，为了有效地靶向质粒DNA，不仅需要优化载体上的配体的性质，而且还需要优化复合物的脂质组成和物理化学性质。总之，我们开发了一种新的细胞选择性药物和基因载体，可以控制药物和基因的生物分布。

Although liposomes are focused on the drug and gene carriers, it is essential to develop the novel effective and cell-selective carrier systems for the clinical application of the various types of drugs. In the present study, we evaluated the novel surface modified liposomes for the purpose of development the advanced liposomes, which possessed the cell-selective properties or controlled interaction with endogenous component. In the present study, we synthesized novel galactosylated and mannosylated cholesterol derivatives for drug and gene delivery to liver parenchymal cell and non-parenchymal cell, respectively. These derivatives possess bi-functional properties i.e. cholesterol for the fix the sugar moiety on liposomal surface and a sugar residue for the cell surface receptors. In vitro study demonstrated that the glycosylated liposomes were efficiently taken up the receptor-mediated endocytosis. After intravenous administration, glycosylated liposomes were effectively taken up by the cells, which expressed the receptor. We also prepared the glycosylated cationic liposomes/plasmid DNA complexes for the liver cell-selective gene delivery. Receptor-mediated gene delivery systems are able to introduce foreign DNA into specific cell types in vivo. However, we have confirmed that not only the nature of the ligands grafted to carriers but also the lipid composition and physicochemical properties of the complexes need to be optimized for effective cell-selective targeting of plasmid DNA. In conclusion, we developed the novel cell-selective drug and gene carriers, which can be controlled the biodistribution of drug and gene.