title: Aerosol delivery of spermine-based poly(amino ester)/Akt1 shRNA complexes for lung cancer gene therapy.
abstract: Polyethylenimine (PEI) has been commonly used as a cationic polymeric gene carrier due to high transfection efficiency, however, its cytotoxicity has hindered the practical application. In this study, we report the development of poly(amino ester) (PAE) based on glycerol propoxylate triacrylate (GPT) and spermine (SPE) as an alternative gene carrier for lung cancer therapy. GPT-SPE copolymer was prepared by Michael addition reaction between GPT and SPE, and the efficacy was evaluated using shAkt1 as a model therapeutic gene. The molecular weight and composition were characterized using gel permeability chromatography (GPC) and (1)H-nuclear magnetic resonance ((1)H-NMR), respectively. The GPT-SPE could effectively condense DNA with about 163 nm size and protect the DNA from nucleases. GPT-SPE/DNA complexes showed excellent transfection with low toxicity both in vitro and in vivo. Furthermore, aerosol delivery of GPT-SPE/Akt1 shRNA complexes significantly suppressed lung tumorigenesis in K-ras(LA1) lung cancer model mice. These results suggest that GPT-SPE can be used in shRNA-based lung cancer gene therapy.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Hong
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Mohammad Ariful
authors.initials: MA
authors.lastname: Islam
authors.forename: Hye-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
authors.forename: Jae-Woon
authors.initials: JW
authors.lastname: Nah
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Ki-Won
authors.initials: KW
authors.lastname: Han
authors.forename: Chanhee
authors.initials: C
authors.lastname: Chae
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000179:Acrylates / Q000737:chemistry / Q000627:therapeutic use*; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000077192:Adenocarcinoma of Lung; D000336:Aerosols; D000818:Animals; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000627:therapeutic use*; D004247:DNA / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D011091:Polyesters / Q000737:chemistry / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000627:therapeutic use*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D034741:RNA, Small Interfering / Q000737:chemistry / Q000627:therapeutic use; D012995:Solubility; D013096:Spermine / Q000737:chemistry / Q000627:therapeutic use*; D014162:Transfection; D047368:Tumor Burden
chemical_list: D000179:Acrylates; D000336:Aerosols; D003432:Cross-Linking Reagents; D011091:Polyesters; D034741:RNA, Small Interfering; D013096:Spermine; D004247:DNA; D051057:Proto-Oncogene Proteins c-akt; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)