Self-Assembled Cationic Micelles Based on PEG-PLL-PLLeu Hybrid Polypeptides as Highly Effective Gene Vectors

Developing safe and, effective. nonviral gene vector is. highly crucial for successful gene therapy. In the designed a series' Of biodegradable :micelles based on hybrid polypeptide copolymers of poly(ethylene glycol)-b-poly(L-lysine)-b-poly(L-leucine) (PEG-PLL-PLLeu) for efficient gene delivery. A group of amphiphilic PEG-PLL-PLLeu: hybrid polypeptide copolymers were synthesized by ring-opening polymerization of N-carboxyanhydride, and the chemical structure Of each copolymer was characterized by H-1 NMR, and FT-IR spectroscopy measurement The PEG-PLL-PLLeu micelles were positively charged with tunable sizes ranging from 40 to 90 nm depending on the length of PLL and PLLeu segment. Compared with PEG-PLL copolymers, PEG-PLL-PLLeu micelles demonstrated significantly higher transfection efficiency and less cytotoxicity Furthermore, the transfection efficiency and biocompatibility of the micelles can be simultaneously improved by tuning the length:of PLL and PLLeu segments. The transfection efficiency of PEG-PLL-PLLeu micelles in Vivo was two to three times higher than that of PEI25k, which was attributable to their capability of promoting DNA condensation and cell internalization is well as successful lysosome: escape Hence well-defined PEG-PLL-PLLeu Micelles would serve as highly effective nonviral. vectors for in vivo :gene delivery..