Folate Receptor Targeting and Cathepsin B-Sensitive Drug Delivery System for Selective Cancer Cell Death and Imaging

被引：32

作者：

Jin, Xiangmei ^{[1
]}

Zhang, Jun ^{[2
]}

Jin, Xiaoyan ^{[1
]}

Liu, Lan ^{[2
]}

Tian, Xizhe ^{[1
]}

机构：

[1] Yanbian Univ, Dept Chem, Yanji 133000, Jilin, Peoples R China

[2] Yanbian Univ, Affiliated Hosp, Dept Pathol, Yanji 133000, Jilin, Peoples R China

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2020年 / 11卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Drug delivery system; folate receptor; cathepsin B; rhodamine B; SN38; IN-VITRO; LIPID NANOPARTICLES; TUMOR; CAMPTOTHECIN; DOXORUBICIN; PACLITAXEL; PRODRUGS; GROWTH; GENE; PH;

D O I：

10.1021/acsmedchemlett.0c00031

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 IC50 values of 2-3 mu M, 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.

引用

页码：1514 / 1520

页数：7