| With the rapid development of biotechnology,gene therapy plays more and more important roles in oncotherapy.The gene vector is the key point of gene therapy,which contains two categories:viral vector and nonviral vector.Viral vector has unavoidable problems because of its toxicity and immunogenicity,thus,nonviral vector-mediated gene delivery has been applied more and more widely during gene therapy.However,a crucial bottleneck in nonviral vector-mediated gene delivery reduces the transfection efficiency,which is poor endosomal escape.Recently,an emerging theme of gene delivery is that some antimicrobial peptides could be used in gene delivery.Antimicrobial peptides could greatly improve the transfection efficiency through their high membrane-lytic activity.Here,we constructed novel gene vectors by coupling the stearyl moiety to the N-terminus of the antimicrobial peptide melittin and its retro isomer.As expected,18-Mel showed obvious increases in endosome-lytic activity and transfection efficiency compared with the reported stearyl-TP10.More interesting,the transfection efficiency of 18-rMel was around 10-fold greater than that of 18-Mel and almost reached the transfection levels of Lipofectamine 2000 due to the enhanced endosome-lytic activity.In addition,the 18-rMel/p53 plasmid complex exhibited higher p53 expression and antitumor activity than 18-Mel,confirming the fact that 18-rMel displayed higher transfection efficiency and potentially becoming an excellent gene vector.In short,the combination of the stearyl moiety with retro melittin provides novel information for the development of gene vectors research,and offers significant theoretical foundation of gene therapy. |
