Multifunctional Tumor-Targeting Cathepsin B-Sensitive Gemcitabine Prodrug Covalently Targets Albumin in Situ and Improves Cancer Therapy

作者:Zhang, Huicong; Su, Zhisu; Wang, Kuanglei; Li, Na; Chen, Hongxiang; Tan, Xiao; Li, Lingxiao; He, Zhonggui*; Sun, Jin*
来源:Bioconjugate Chemistry, 2018, 29(6): 1852-1858.
DOI:10.1021/acs.bioconjchem.8b00223

摘要

We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting, and site-specific drug release are achieved, and as such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.