Rational Design of Intracellular Anticancer Drug Delivery: Nanocarriers Bearing Two-step Degradation Mechanism

合成了一种谷胱甘肽-对硝基苯胺缀合物，并对其与谷胱甘肽s -转移酶（GST）的结合进行了研究。当用GST滴定共轭物时，吸光度随GST浓度的增加而增加，表明共轭物与GST结合。此外，在GST存在下观察到对硝基苯胺的释放。对于前体药物的纳米载体设计，研究了聚甘油树状大分子（PGDs），以阐明它们与抗癌药物5-氟尿嘧啶（5-Fu）的相互作用。19F- nmr、1H-NMR和荧光光谱结果证实PGD在水溶液条件下可以包封5-Fu。另一个纳米载体制剂的检查，脂质体组成的pgd为基础的磷脂和聚合物胶束组成的维生素E和生物相容性聚合物。通过这些研究，新型智能纳米载体与produg系统结合在GST靶向上是可行的。

A glutathione-p-nitroaniline conjugate was synthesized and examined binding of the conjugate with glutathione S-transferase (GST). When the conjugate was titrated with GST, absorbance increased with increasing concentration of GST, suggesting the binding the conjugate with GST. In addition, p-nitroaniline release was observed in the presence of GST. As for the design of nanocarriers for the prodrug, polyglycerol dendrimers (PGDs) were subjected and examined to clarify their interaction with the anti-cancer drug, 5-fluorouracil (5-Fu). The results of 19F-, 1H-NMR and fluorescence spectroscopy to confirm that PGD could encapsulate 5-Fu under aqueous conditions. Another examination of nanocarrier preparations, a liposome consisting of PGD-based phospholipids and a polymeric micelle consisting of vitamin E and a biocompatible polymer.Through these studies, novel smart nanocarries in combination with the produg system toward GST targeting are feasible in near future.