High-performance cationic polyrotaxanes terminated with polypeptides as promising nucleic acid delivery systems

Abstract

Nucleic acid (NA)-based therapy was put forward as a promising method to conquer serious human diseases. Safe and robust gene vectors play an important role in NA delivery processes. In this work, a novel ABA-triblock hydroxyl-rich cationic polyrotaxane PP-PGEA, consisting of one polyethylene glycol backbone, CD-PGEA (composed of one cyclodextrin (CD) core and three ethanolamine (EA)-functionalized poly(glycidyl methacrylate) arms) assembly units, and degradable end-capping polypeptide segments, was prepared as a promising NA delivery system. PP-PGEA has low cytotoxicity and degradability, beneficial to the NA delivery process. The breakdown of end-capping polypeptides could benefit the disassembly of PP-PGEA within cells. PP-PGEA demonstrated substantially higher transfection performances than CD-PGEA assembly units. PP-PGEA was also shown to possess remarkable anti-cancer capability through glioma models. Such a high-performance cationic polyrotaxane with terminal polypeptides would provide a very promising means to produce efficient delivery vectors of versatile NAs.