title: Suppression of lung cancer progression by biocompatible glycerol triacrylate-spermine-mediated delivery of shAkt1.
abstract: BACKGROUND
  Polyethylenimine (PEI)-based nonviral gene-delivery systems are commonly employed because of their high transfection efficiency. However, the toxic nature of PEI is a significant obstacle in clinical gene therapy. In this study, we developed biocompatible glycerol triacrylate-spermine (GT-SPE) polyspermine as a nanosized gene carrier for potential lung cancer gene therapy.
  
  
  METHODS
  The GT-SPE was synthesized using the Michael addition reaction between GT and SPE. The molecular weight was characterized using gel permeability chromatography multiangle laser light scattering and the composition of the polymer was analyzed using proton nuclear magnetic resonance.
  
  
  RESULTS
  The GT-SPE successfully protected the DNA from nucleases. The average particle size of the GT-SPE was 121 nm with a zeta potential of +23.45 mV. The GT-SPE was found to be less toxic than PEI for various cell lines, as well as for a murine model. Finally, our results showed that the GT-SPE/small hairpin Akt1 (shAkt1) complex suppressed lung tumorigenesis in a K-ras(LA1) lung cancer mice model by inducing apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol delivered GT-SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and suppressed the expression levels of proliferating cell nuclear antigen, as well as vascular endothelial growth factors and CD31, which are known proliferation and angiogenesis markers, respectively.
  
  
  CONCLUSIONS
  Our data suggest that GT-SPE may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene therapy.
authors.affiliation: Laboratory of Toxicology, Seoul National University, Seoul, Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Hong
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Shin
authors.forename: Bitna
authors.initials: B
authors.lastname: Kang
authors.forename: Hye-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.forename: Chanhee
authors.initials: C
authors.lastname: Chae
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000336:Aerosols; D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005990:Glycerol; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D050997:Nanomedicine; D049329:Nanostructures / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics* / Q000627:therapeutic use; D013096:Spermine; D014162:Transfection
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D034741:RNA, Small Interfering; D013096:Spermine; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9; D005990:Glycerol