新型双联肽-藤黄酸前体药物构建及其抗膀胱癌作用研究

找到一种对肿瘤细胞具有高选择性的治疗方法尤为重要，内切蛋白酶激活型肿瘤前体药物就是其中一种极具前景的治疗策略。Legumain是新发现的半胱氨酸蛋白酶,在肿瘤组织微环境特异性高表达，而且其酶切反应中对反应底物有独特高选择性要求，使它成为一个富有吸引力的抗肿瘤前药激活酶的候选。本课题通过将legumain切割底物与穿膜肽Tat相连接，制备创新性双联肽分子；继而将新型药物藤黄酸与双联肽分子偶联，形成双联肽靶标前体药物。该前体药物特异地在肿瘤组织中被切割释放，从而具有靶向性；同时穿膜肽Tat增加了药物对肿瘤细胞的穿透杀伤效果，使藤黄酸抗肿瘤作用需要的药物浓度有效降低。本研究的成功实施将为膀胱癌的高效特异性主动靶向治疗提供实验基础。

To find a highly selective treatment of tumor cells is particularly important. Tumor specific endo-protease activated prodrug is a promising treatment strategy. Legumain is a newly discovered cysteine protease that highly expressed in the tumor microenvironment, coupled with the digestion reaction on a substrate with a unique high selectivity requirement, making it an attractive drug activation enzyme candidate. This subject will construct an innovative double coupling peptides based on legumain cutting the substrate and tat peptide penetrating the cell membrane.Then, garcinia acid will be linked to the double coupling peptides to create a novel drugs. The drug precursor will be specifically cut and released in tumor tissue, and be carried by the tat peptide into the cancer cells, so that the effective concentration of anti-tumor effect of Garcinia acid will greatly reduced. The successful implementation of this project will provide an efficient specific and initiative targeted therapy for the bladder cancer.