Arginine-rich peptide based nanoparticles with bridge-like structure: enhanced cell penetration and tumor therapy effect

Gene therapy has been recognized as one of the most potential approaches on cancer treatment field. Arginine-rich cell penetrating peptides have attracted enormous interests in gene delivery field due to their superior membrane translocation capability. Herein, we developed a novel arginine-rich peptide based gene delivery system consisted of tri-block copolymers C7F15-R(HR)(5)K-C7F15. The tri-block copolymers would assemble into nanoparticles in aqueous solution with special bridge-like structure denoted as NPT. At the same time, di-block copolymers Ac-R(HR)(5)K-C7F15 were constructed and assembled into nanoparticles named NPD as control. The bridge-like structure extremely promoted interaction efficiency of arginine residues and cell membrane leading to enhanced endocytosis and gene transfection efficiency. Compared with NPD of traditional structure, NPT exhibited superior in vitro gene transfection efficiency which was two fold higher than NPD. Anti-epidermal growth factor receptor (EGFR)-shRNA loaded NPT caused 95% apoptosis of MCF-7 cells and significant tumor inhibition effect with neglected toxicity. These may help NPT step forward to further application.