Intelligent approach to construct intravenously injectable nanoparticles by interface transference properties

在目前的研究中，开发人造红细胞或人造血小板所积累的知识是被利用的。我们通过一种简单的方法将由受体蛋白、多肽或糖链等配体组成的识别位点引入到这些纳米粒子的表面，旨在使其在医疗上变得智能和有效。2003年，我们合成了大量的双链氨基酸型脂类化合物，并用固相合成法研究了这些类脂类化合物与寡肽或寡糖的偶联方法。然后，我们得到了含有两个或四个烷基的聚乙二醇脂。此外，以α-马来酰亚胺、ω-琥珀酰亚胺聚乙二醇酯为原料，大规模合成了功能性聚乙二醇脂。此外，我们还将二硫键上的烷基链偶联为膜膨胀填料，并在末端与马来酰亚胺聚乙二醇酯偶联，合成了功能性聚乙二醇脂。接下来，对于…为使脂多糖作为生物活性物质污染更多的脂质体，采用表面活性剂处理，利用界面转移现象定量测定脂多糖的含量。2004年，通过界面转移的方法将马来酰亚胺聚乙二醇脂引入脂质体表面。然后，将相对分子质量不同的蛋白质(乳清蛋白(Mw：14 kDa)、重组人血清白蛋白(RHSA)(66.5 kDa)、免疫球蛋白(Ig G，150 kDa)、铁蛋白(Ferritin，460 kDa)、甲状腺球蛋白(Thyrogroblin，670 kDa))结合到聚乙二醇脂中，分析从脂质体表面分离出的蛋白质脂的比例。结果表明，聚乙二醇脂中烷基链的数目和长度与蛋白质的相对分子质量有很好的相关性。此外，如果识别分子(糖或寡肽)偶联在脂质体表面，然后用聚乙二醇链修饰，识别能力被认为是被聚乙二醇链掩盖的。然而，研究表明，当聚乙二醇脂类从表面分离(界面转移)时，功能表达发生了转换。根据以上结果，可以利用脂质体表面修饰的聚乙二醇脂或蛋白质偶联聚乙二醇脂的隔离现象，设计出可控制药物动力学的新型药物载体。较少

In present study, the knowledge accumulated by development of an artificial red blood cell or artificial platelets is exploited. We incorporated the recognition sites, which were made of ligands such as receptor proteins and peptides or sugar chains, into the surface of these nano-particles by a simple method, aiming to making it intelligent and effective in a medical treatment. In 2003, we synthesized the large amount of the amino acid-type lipids with two chains, and examined the conjugation method of these lipids to oligopeptides or oligosaccharides by a solid-phase synthesis method. Then, we obtained the polyethyleneglycol-lipids with two or four alkyl chains. Furthermore, the functional PEG-lipid was synthesized in a large scale from a-maleimide, ω-succinimide PEG. Moreover, we also synthesized the functional PEG-lipids by coupling the alkyl chains in the disulfides bond as being considered as the membrane expanding packing, and combined maleimide PEG at the terminal. Next, for th … More e liposomes contaminated with lipopolysaccharide(LPS) as a bioactive substance, a surfactant treatment was applied to quantitatively measure the LPS content by using the interfacial transfer phenomenon. In 2004, the maleimide PEG lipid was introduced on the liposome surface by the interfacial transfer method. Then, proteins of which molecular weight was different (Lactalbumin(Mw : 14kDa), rHSA (66.5kDa), IgG (150kDa), Ferritin (460kDa), and Thyrogrobulin (670kDa)) were combined to the PEG lipid and the rate of the resulting protein-lipids isolated from the liposome surface (interfacial transfer) was analyzed. As a result, good correlation was acquired between the number and length of the alkyl chains of the PEG lipid, and the protein molecular weight. Moreover, if a recognition molecule (saccharide or oligopeptide) is conjugated on the liposome surface and then modified with PEG chains, the recognition ability is considered to be masked with the PEG chain. However, it was clarified that functional expression was switched when PEG lipids was isolated from the surface (interfacial transfer). From the above results, the novel drug carriers which can control pharmacokinetic can be designed by utilizing the isolation phenomenon of the PEG-lipids or protein-conjugated PEG-lipids modifying the liposome surface. Less