title: Effective tumor treatment by VEGF siRNA complexed with hydrophobic poly(amino acid)-modified polyethylenimine.
abstract: Two copolymers are designed and synthesised for siRNA delivery based on polyethylenimine by grafting hydrophilic acrylamide segments and hydrophobic poly(γ-benzyl L-glutamate). The amphiphilic PEI-PBLG/siRNA complex demonstrates high gene silencing efficiency in the absence or presence of 10 vol% and 50 vol% sera in vitro. The anti-tumor effects in vivo are evaluated in luciferase-bearing mice expressing CT26 tumors. PEI-PBLG/siVEGF complex provides a higher and more sustained suppressive effect by reducing VEGF mRNA expression in the tumors, leading to higher tumor growth inhibition efficacy. Further studies on the potential use of the PEI-PBLG carrier system in mediating the silencing of genes other than VEGF or in other tumor models are recommended.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Huayu
authors.initials: H
authors.lastname: Tian
authors.forename: Xuan
authors.initials: X
authors.lastname: Dong
authors.forename: Zhaopei
authors.initials: Z
authors.lastname: Guo
authors.forename: Zixue
authors.initials: Z
authors.lastname: Jiao
authors.forename: Feifan
authors.initials: F
authors.lastname: Li
authors.forename: Arihiro
authors.initials: A
authors.lastname: Kano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maruyama
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D011108:Polymers; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C521445:polyethylenimine-poly(gamma-benzylglutamate); D011099:Polyglutamic Acid; D011094:Polyethyleneimine
keywords: RNA; amphiphiles; anti-tumor; gene therapy; hydrophilic polymers