title: Self-assembled cationic micelles based on PEG-PLL-PLLeu hybrid polypeptides as highly effective gene vectors.
abstract: Developing safe and effective nonviral gene vector is highly crucial for successful gene therapy. In the present study, we 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 (1)H 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 PEI(25k), which was attributable to their capability of promoting DNA condensation and cell internalization as well as successful lysosome escape. Hence well-defined PEG-PLL-PLLeu micelles would serve as highly effective nonviral vectors for in vivo gene delivery.
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Key Laboratory of Cancer Nanotechnology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advance Technology, Chinese Academy of Sciences, PR China.
authors.forename: Jizhe
authors.initials: J
authors.lastname: Deng
authors.forename: Ningning
authors.initials: N
authors.lastname: Gao
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.forename: Huqiang
authors.initials: H
authors.lastname: Yi
authors.forename: Shengtao
authors.initials: S
authors.lastname: Fang
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
mesh_terms: D002460:Cell Line; D004247:DNA / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry; D008823:Micelles; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis; D013501:Surface-Active Agents / Q000737:chemistry; D014162:Transfection
chemical_list: D008823:Micelles; D010455:Peptides; D011108:Polymers; D013501:Surface-Active Agents; C092361:poly(ethylene glycol) lysine copolymer; C027819:polyleucine; D011092:Polyethylene Glycols; D004247:DNA; D008239:Lysine