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Poly(ester amine)-mediated, Aerosol-delivered Akt1 Small Interfering RNA Suppresses Lung Tumorigenesis

¹ Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea; ² Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea; ³ Center for Developmental Pharmacology and Toxicology, Seattle Children's Hospital Research Institute, Seattle, Washington; ⁴ Nano Systems Institute–National Core Research Center, Seoul National University, Seoul, Korea; ⁵ Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea; ⁶ Laboratory of Molecular Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea; ⁷ Division of Endocrinology, Metabolism, and Lipids, Emory University School of Medicine, Atlanta, Georgia; and ⁸ National Institute of Toxicological Research, Seoul, Korea

Correspondence and requests for reprints should be addressed to Myung-Haing Cho, D.V.M., Ph.D., Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea. E-mail: mchotox{at}snu.ac.kr or Chong-Su Cho at chocs{at}snu.ac.kr

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.

Key Words: poly(ester amine) • Akt1 siRNA • lung cancer • K-ras^LA1 mice • urethane • aerosol gene delivery

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Recent advances in aerosol-mediated gene delivery suggest that this approach may be useful in the treatment of lung cancer. What This Study Adds to the Field Poly(ester amine) carrier may serve as an effective carrier, and aerosol delivery of Akt1 small interfering RNA may be a promising approach for lung cancer treatment and prevention.