Creation ofPolumeric Drugs and Drug Carriers Possessing Pilot Molecules on the Surface and Their Application for Targeting Therapy

我们一直专注于几种类型的杂远螺旋聚乙二醇的合成，这意味着PEG在一端具有一个官能团，在另一端具有另一个官能团，选择性和定量。利用这些异聚乙二醇，制备了乳糖- peg - sod偶联物。发现该偶联物通过受体介导的内吞作用优先与HepG2和HL60等肝细胞结合。以异聚乙二醇为大引发剂进行阴离子开环聚合，合成了聚乙二醇链端具有官能团的聚乙二醇/聚乳酸两亲性嵌段共聚物。嵌段共聚物在几十纳米大小的水介质中形成核-壳型聚合物胶束。核-壳型聚合物胶束可以溶解疏水药物，增加药物在血液中的循环，并通过胶束的亲水外壳将药物与血液和组织分离，从而降低药物的毒性。因此，聚合物胶束-药物配合物在药物效率方面表现出显著的改善，有望成为下一代新型纳米技术科学之一。由此制备的聚合物胶束最重要的点是胶束的表面。由于PEG链端位于胶束的外围，因此表面应被PEG端基功能化。在聚乙二醇/聚乳酸胶束表面安装了几种配体。最后，我们观察到胶束表面配体与受体的特异性相互作用，不仅是蛋白质，而且是特定的细胞。在研究的基础上，将开辟新的主动定位技术。

We have been focusing on synthesis of several types of heterotelechelic poly(ethylene glycol), which denotes PEG possessing a functional group at one end and another functional group at the other chain end, both selectively and quantitatively. Utilizing these heteroPEG, lactose-PEG-SOD conjugate were prepared. The conjugate was found to incorporate preferentially to hepatocells such as HepG2 and HL60, via receptor mediated endocytosis.Using heteroPEG as macroinitiator for an anionic ring opening polymerization of lactide, PEG/PLA amphiphilic block copolymers possessing a functional group at PEG chain end were synthesized. The block copolymer forms core-shell type polymeric micelle in aqueous media having several tens nanometer size. The core-shell type polymeric micelle can solubilize hydrophobic drugs, which increases drug circulation in blood stream and reduces a toxicity of the drug due to the separation of the drug from the blood and tissues by the hydrophilic shell of the micelle. Consequently, polymer micelle-drug complexes show remarkable improvement in drug efficiencies, which is anticipated as one of the new nano-technology sciences for next generation.The most important point of the polymeric micelles thus prepared was the surface of the micelle. Since the PEG chain end locates on the periphery of the micelle, the surface should be functionalized by the PEG end group. Several ligands were installed on the surface of the PEG/PLA micelle. Finally, we observed specific interaction of the ligands on the micelle surface and receptor not only protein but also specific cells.On the basis of the investigations, new active targeting techniques will be opened.