Supramolecular assembly of protein-based nanoparticles based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for cancer therapy

Abstract Molecular self-assembly of functional proteins has garnered intense interest for the development of nanomaterials. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as one of the most promising agents for cancer therapy, could selectively induce the apoptotic cell death in tumor cells while not on normal cells. In this study, protein-based nanoparticles were constructed with TRAIL and a dipeptide, diphenylalanine (FF), through molecular self-assembly. TRAIL-FF nanoparticles with sizes ranging from 60 nm to 500 nm could be prepared by controlling the concentration and the ratio of the two components. These nanoparticles could locate around the cytomembrane of MCF-7 cells due to the specific interaction between TRAIL and death receptors, thus transduce apoptotic signal. Therefore, the TRAIL-FF nanoparticles showed distinct killing effect on the cancer cells, such as MCF-7 and H460 cells, and the IC50 of the nanoparticles on H460 cells was about 260 ng/mL. The approach presented herein may be applicable to the fabrication of an extended range of protein-based functional biomaterials.