title: Polylysine-modified polyethylenimine inducing tumor apoptosis as an efficient gene carrier.
abstract: Polyethylenimine (PEI) is receiving increasing attention as a gene carrier with high transfection efficiency. However, its high charge density and cytotoxic effects limit its application. Polylysine (PLL) is another polymeric gene carrier with good biodegradability and biocompatibility, although its lack of endosomal escape ability strongly impairs its transfection efficiency. In this study, PLL was introduced to PEI by ring-opening polymerization of ε-benzyloxycarbonyl-l-lysine N-carboxyanhydride, followed by deprotection of carbobenzyloxy groups. As-prepared PEI-PLL multiarm hyperbranched copolymers were characterized as gene carriers in vitro by measuring their particle size, zeta potential, cytotoxicity, transfection efficiency, and cell internalization. The optimum transfected efficiency of PEI-PLL was nearly seven times higher than that of PEI with a molecular weight of 25kDa. Furthermore, pKH3-rev-casp-3 plasmid DNA was used as a gene for anti-tumor treatment in a xenograft model using nude mice. Compared with 25kDa PEI, PEI-PLL exhibited better tumor inhibition effects in 23days. In addition, terminal deoxynucleotidyl transferase dUTP nick end labeling, immunohistochemistry, and western blot analysis were used to determine the anti-tumor mechanism of PEI-PLL. The results showed that tumor cell apoptosis led to tumor inhibition, which could be attributed to pKH3-rev-casp-3 inducing poly(ADP-ribose) polymerase-1 cleavage. PEI-PLL is a promising gene carrier candidate for further application in vivo.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Huayu
authors.initials: H
authors.lastname: Tian
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Zixue
authors.initials: Z
authors.lastname: Jiao
authors.forename: Zhaopei
authors.initials: Z
authors.lastname: Guo
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Shiqian
authors.initials: S
authors.lastname: Gao
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics; D004247:DNA / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000737:chemistry* / Q000633:toxicity; D011107:Polylysine / Q000737:chemistry* / Q000633:toxicity; D014162:Transfection / Q000379:methods*
chemical_list: D011107:Polylysine; D011094:Polyethyleneimine; D004247:DNA; D053148:Caspase 3
keywords: Apoptosis; Gene delivery; Polyethylenimine; Polylysine; Tumor inhibition