去氢骆驼蓬碱为新疆特有维吾尔习用药，其能有效地治疗肝肿瘤和消化道肿瘤等多种肿瘤，因存在神经系统毒副作用，其应用受到限制。本课题在前期基础上，基于肿瘤细胞表面和肿瘤相关巨噬细胞表面高表达legumain酶，且legumain酶对AAN肽序列有专一水解作用的特点，结合磁纳米粒的靶向性，设计一种去氢骆驼蓬碱双靶向前药系统，该系统利用去氢骆驼蓬碱9位仲胺基可修饰且为活性位点的特点，将去氢骆驼蓬碱与AAN肽偶联，再在AAN另一端偶联磁纳米粒，生成去氢骆驼蓬碱-AAN-磁纳米粒复合物，该复合物在体内，因去氢骆驼蓬碱结构发生变化，导致其不会产生神经系统毒副作用，类似于前药，并借磁纳米粒和legumain的双重靶向到达肿瘤细胞，在肿瘤细胞，肿瘤表面的legumain酶将去氢骆驼蓬碱与磁纳米粒断裂，药物进入肿瘤细胞发挥作用。该系统利用分子靶向和磁靶向双重靶向作用，结合前药原理，有效达到高效减毒效果。

Harmine is a uygur anti-cancer drug, it has effect on liver tumor, but it has no preparations now because of its toxic to nerve system. In this study, a new harmine dual-targeted prodrug system was prepared. Legumain is a highly conserved lysosomal/vascuolar cysteine protease, which is primarily expressed in tumor cell and tumor associated macrophages. Also, Legumain is reported to cleave C-terminally aspartate(Asn) residues at pH below 5. Furthermore, Magnetic nanoparticles has many advantages in drug delivery，it can target to tumor when some magnetic field is put in tumor in vitro. So according to those backgrounds, a kind of dual-targeted harmaine prodrug system was prepared, in which harmine was conjugated with AAN peptide because the carboxyl group of AAN would react with amine of harmine , and then AAN peptide was conjugated with magnetic nanoparticles. When this kind of harmine-AAN-magnetic nanoparticles complex was given, harmine had no side effects because its structure changed and harmine would accumulate in tumor with the help of magentic targeting and legumain targeting. After harmine arrived at tumor, harmine released and took its anti-tumor effect because legumain hydrolyzed AAN peptide in tumor. This system had dual-targeted effect, whcih would be targeted into tumor because of legumain and magnetic nanoparticles and then the side-effect of harmine would be decreased too.