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

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.