Jin Xiangmei, Zhang Jun, Jin Xiaoyan, Liu Lan, Tian Xizhe
Department of Chemistry, Yanbian University, Yanji 133000, Jilin, China.
Department of Pathology, Affiliated Hospital of Yanbian University, Yanji 133000, Jilin, China.
ACS Med Chem Lett. 2020 May 18;11(8):1514-1520. doi: 10.1021/acsmedchemlett.0c00031. eCollection 2020 Aug 13.
In this work, a folate receptor (FR)-mediated dual-targeting drug delivery system was synthesized to improve the tumor-killing efficiency and inhibit the side effects of anticancer drugs. We designed and synthesized an FR-mediated fluorescence probe (FA-Rho) and FR-mediated cathepsin B-sensitive drug delivery system (FA-GFLG-SN38). FA-GFLG-SN38 is composed of the FR ligand (folic acid, FA), the tetrapeptide substrate for cathepsin B (GFLG), and an anticancer drug (SN38). The rhodamine B (Rho)-labeled probe FA-Rho is suitable for specific fluorescence imaging of SK-Hep-1 cells overexpressing FR and inactive in FR-negative A549 and 16-HBE cells. FA-GFLG-SN38 exhibited strong cytotoxicity against FR-overexpressing SK-Hep-1, HeLa, and Siha cells, with IC values of 2-3 μM, but had no effect on FR-negative A549 and 16-HBE cells. The experimental results show that the FA-CFLG-SN38 drug delivery system proposed by us can effectively inhibit tumor proliferation in vitro, and it can be adopted for the diagnostics of tumor tissues and provide a basis for effective tumor therapy.
在本研究中，合成了一种叶酸受体（FR）介导的双靶向药物递送系统，以提高肿瘤杀伤效率并抑制抗癌药物的副作用。我们设计并合成了一种FR介导的荧光探针（FA-Rho）和一种FR介导的组织蛋白酶B敏感型药物递送系统（FA-GFLG-SN38）。FA-GFLG-SN38由FR配体（叶酸，FA）、组织蛋白酶B的四肽底物（GFLG）和一种抗癌药物（SN38）组成。罗丹明B（Rho）标记的探针FA-Rho适用于对过表达FR的SK-Hep-1细胞进行特异性荧光成像，而在FR阴性的A549和16-HBE细胞中无活性。FA-GFLG-SN38对过表达FR的SK-Hep-1、HeLa和Siha细胞表现出较强的细胞毒性，IC值为2-3 μM，但对FR阴性的A549和16-HBE细胞无影响。实验结果表明，我们提出的FA-CFLG-SN38药物递送系统能够在体外有效抑制肿瘤增殖，可用于肿瘤组织的诊断，并为有效的肿瘤治疗提供依据。
