豆荚蛋白酶(legumain)是一种天冬氨酸内切酶,在一些高转移性和高侵袭性肿瘤中高表达,能水解特定的多肽底物。基于此,本文构建了一种豆荚蛋白酶响应的功能化金纳米粒递药系统(GNPs-A&C),由丙氨酸-丙氨酸-天冬酰胺-半胱氨酸-赖氨酸(AK多肽)修饰的金纳米粒(GNPs-AK)与2-氰基-6-氨基苯并噻唑(CABT)修饰的金纳米粒(GNPs-CABT)组成。GNPs-A&C进入血液循环后可以通过增强的渗透和滞留(EPR)效应到达肿瘤部位并渗透进入内部,在肿瘤高表达的豆荚蛋白酶作用下内切AK序列,暴露出半胱氨酸上的1,2-巯基氨基,进而与CABT上的氰基发生点击反应,引起纳米粒聚集,形成粒径更大的聚集体,更好滞留在肿瘤内部。活体成像表明,GNPs-A&C在豆荚蛋白酶高表达的脑胶质瘤(C6)中具有良好的靶向性和蓄积能力,同时载有多柔比星(DOX)功能化金纳米粒递药系统(GNPs-DOX-A&C)展示了显著的抗肿瘤效果并降低了DOX的心肌毒性。 Legumain, an aspartic endonuclease, is overexpressed in some highly metastatic and highly aggressive tumors and can hydrolyze specific polypeptide substrates. Based on this, we constructed a pod protease-responsive functionalized gold nanoparticle drug delivery system (GNPs-A & C) consisting of alanine-alanine-asparagine-cysteine-lysine ) Modified gold nanoparticles (GNPs-AK) and 2-cyano-6-aminobenzothiazole (CABT) modified gold nanoparticles (GNPs- CABT). After entering the blood circulation, GNPs-A & C can reach the tumor site through the enhanced infiltration and retention (EPR) effect and infiltrate into the interior. The AK sequence is endocytosed by the pod protease highly expressed by the tumor, exposing the cysteine ​​1, 2-mercaptoamino, and then click reaction with the cyano group on the CABT, causing the nanoparticles to aggregate, forming larger aggregates, better retention in the tumor. In vivo imaging showed that GNPs-A & C has good targeting and accumulation capacity in pod protease-overexpressing glioma (C6), and at the same time contains doxorubicin (DOX) functionalized gold nanoparticle drug delivery system GNPs-DOX-A & C) demonstrated significant antitumor effects and reduced cardiotoxicity of DOX.