1. ¹Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea
2. ²Nano Systems Institute-National Core Research Center, Seoul National University, Seoul, Korea
3. ³Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea
4. ⁴School of Veterinary Medicine, Kangwon National University, Chuncheon, Korea
5. ⁵Laboratory of Molecular Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
6. ⁶Laboratory of Biomedical Polymer and Tissue Engineering, School of Agricultural Biotechnology, Seoul National University, Seoul, Korea

Correspondence: Professor M-H Cho, Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea. E-mail: mchotox@snu.ac.kr; Professor C-S Cho, Laboratory of Biomedical Polymer and Tissue Engineering, School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea. E-mail: chocs@plaza.snu.ac.kr

⁷Current address: Center for Developmental Pharmacology and Toxicology, Seattle Children's Hospital Research Institute, Seattle, Washington 98101, USA

Received 20 August 2007; Revised 1 November 2007; Accepted 25 November 2007; Published online 22 February 2008.

Abstract

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC–PTEN were delivered into K-ras^LA1 lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC–PTEN may be compatible with noninvasive in vivo gene therapy.