Transferrin-conjugated paclitaxel prodrugs for targeted cancer therapy

Abstract

Paclitaxel (PTX) is one of the most effective chemotherapeutic drugs ever developed and is effective against a wide spectrum of tumors. The clinical application of PTX, however, is limited by its severe side effects. We developed new ligand-mediated prodrugs, namely, PTX conjugated with Fmoc-L-glutamic acid 5-tert-butyl ester (linker) and transferrin (Tf, ligand/carriers), to specifically target tumor cells/tissues. PTX was labeled with FITC or a near-infrared (NIR) dye ICG-Der-02, respectively, for in vitro and in vivo imaging studies. MTT assay and apoptosis studies demonstrated that the prodrug had efficient inhibition of tumor cell proliferation with low toxicity to normal cells. More importantly, the prodrug Tf–Glu–PTX displayed a potential to overcome PTX resistance in drug-resistant MDA-MB-231 cell lines. Our in vivo studies also demonstrated that Tf–Glu–PTX significantly decreased side effects and enhanced the antitumor efficiency compared to free PTX. Collectively, our study showed that Tf–Glu–PTX is a promising prodrug for targeted cancer therapy.