title: Poly(ester amine)-mediated, aerosol-delivered Akt1 small interfering RNA suppresses lung tumorigenesis.
abstract: BACKGROUND
  The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for the development of novel therapeutic options. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer.
  
  
  OBJECTIVE
  To demonstrate the feasibility and emphasize the importance of noninvasive aerosol delivery of Akt1 small interfering RNA (siRNA) as an effective and selective option for lung cancer treatment.
  
  
  METHODS
  Nanosized poly(ester amine) polymer was synthesized and used as a gene carrier. An aerosol of poly(ester amine)/Akt1 siRNA complex was delivered into K-ras(LA1) and urethane-induced lung cancer models through a nose-only inhalation system. The effects of Akt1 siRNA on lung cancer progression and Akt-related signals were evaluated.
  
  
  RESULTS
  The aerosol-delivered Akt1 siRNA suppressed lung tumor progression significantly through inhibiting Akt-related signals and cell cycle.
  
  
  CONCLUSIONS
  The use of poly(ester amine) serves as an effective carrier, and aerosol delivery of Akt1 siRNA may be a promising approach for lung cancer treatment and prevention.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
authors.forename: Cheng-Xiong
authors.initials: CX
authors.lastname: Xu
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Jere
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Youn-Sun
authors.initials: YS
authors.lastname: Chung
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Shin
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Lee
authors.forename: Chan-Hee
authors.initials: CH
authors.lastname: Chae
authors.forename: Kee Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: George R
authors.initials: GR
authors.lastname: Beck
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D002273:Carcinogens; D018797:Cell Cycle Proteins / Q000378:metabolism; D004337:Drug Carriers; D011905:Genes, ras; D015316:Genetic Therapy; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D053761:Nanocomposites; D011073:Polyamines; D011091:Polyesters; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014162:Transfection; D014520:Urethane
chemical_list: D000336:Aerosols; D002273:Carcinogens; D018797:Cell Cycle Proteins; D004337:Drug Carriers; D011073:Polyamines; D011091:Polyesters; D034741:RNA, Small Interfering; C516446:poly(caprolactone-block-ethyleneimine); D014520:Urethane; D051057:Proto-Oncogene Proteins c-akt