RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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.
RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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: Lori R Kisley; Bradley S Barrett; Alison K Bauer; Lori D Dwyer-Nield; Benjamin Barthel; Amy M Meyer; David C Thompson; Alvin M Malkinson Journal: Cancer Res Date: 2002-12-01 Impact factor: 12.701
Authors: L A Dailey; E Kleemann; T Merdan; H Petersen; T Schmehl; T Gessler; J Hänze; W Seeger; T Kissel Journal: J Control Release Date: 2004-12-10 Impact factor: 9.776
Authors: Hyun Woo Kim; In Kyu Park; Chong Su Cho; Kee Ho Lee; George R Beck; Nancy H Colburn; Myung Haing Cho Journal: Cancer Res Date: 2004-11-01 Impact factor: 12.701
Authors: Anna A Shvedova; James P Fabisiak; Elena R Kisin; Ashley R Murray; Jenny R Roberts; Yulia Y Tyurina; James M Antonini; Wei Hong Feng; Choudari Kommineni; Jeffrey Reynolds; Aaron Barchowsky; Vince Castranova; Valerian E Kagan Journal: Am J Respir Cell Mol Biol Date: 2007-12-20 Impact factor: 6.914