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Developing safe and effective nonviral gene vector ishighly crucialfor successful gene therapy. In the present study, we designed a seriesof biodegradable micelles based on hybrid polypeptide copolymers ofpoly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) for efficientgene delivery. A group of amphiphilic PEG-PLL-PLLeu hybrid polypeptidecopolymers were synthesized by ring-opening polymerization of N-carboxyanhydride, and the chemical structure of each copolymerwas characterized by 1H NMR and FT-IR spectroscopy measurement.The PEG-PLL-PLLeu micelles were positively charged with tunable sizesranging from 40 to 90 nm depending on the length of PLL and PLLeusegment. Compared with PEG-PLL copolymers, PEG-PLL-PLLeu micellesdemonstrated significantly higher transfection efficiency and lesscytotoxicity. Furthermore, the transfection efficiency and biocompatibilityof the micelles can be simultaneously improved by tuning the lengthof PLL and PLLeu segments. The transfection efficiency of PEG-PLL-PLLeumicelles in vivo was two to three times higher than that of PEI25k, which was attributable to their capability of promotingDNA condensation and cell internalization as well as successful lysosomeescape. Hence well-defined PEG-PLL-PLLeu micelles would serve as highlyeffective nonviral vectors for in vivo gene delivery. [ABSTRACT FROM AUTHOR]

Abstract: Modern subunit vaccines with purified or recombinant antigens are important alternatives to the traditional vaccines. However, there remains a big challenge to elicit potent antibody production and CD8 T cell response. Nanoparticle-based antigen delivery systems have emerged as an innovative strategy to improve the efficacy of subunit vaccines. The present study reported self-assembled cationic micelles based on poly(ethylene glycol)-b-poly(L-lysine)-b-poly(L-leucine) (PEG-PLL-PLLeu) hybrid polypeptides as a simple and potent vaccine delivery system. The results showed that the PEG-PLL-PLLeu micelles spontaneously encapsulated OVA antigens with great loading capacity (LC=55%) and stability. More importantly, the polypeptide micelle formulations robustly enhanced vaccine-induced antibody production by 70–90 fold, which could be due to their capability of inducing dendritic cell maturation, enhancing antigen uptake and presentation, as well as promoting germinal center formation. Furthermore, the polypeptide micelles could simultaneously encapsulate OVA and polyriboinosinic: polyribocytidylic acid (PIC), a TLR3 agonist, to synergistically augment tumor specific cytotoxic-T-lymphocyte (CTL) response. Hence, the polypeptide micelle-based antigen delivery system could be a robust adjuvant to enhance vaccine-induced immune responses. [Copyright &y& Elsevier]