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

Xiangmei Jin; Jun Zhang; Xiaoyan Jin; Lan Liu; Xizhe Tian

doi:10.1021/acsmedchemlett.0c00031

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

ACS Med Chem Lett. 2020 May 18;11(8):1514-1520. doi: 10.1021/acsmedchemlett.0c00031. eCollection 2020 Aug 13.

Authors

Xiangmei Jin¹, Jun Zhang², Xiaoyan Jin¹, Lan Liu², Xizhe Tian¹

Affiliations

¹ Department of Chemistry, Yanbian University, Yanji 133000, Jilin, China.
² Department of Pathology, Affiliated Hospital of Yanbian University, Yanji 133000, Jilin, China.

Abstract

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 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.