期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 420, 期 2, 页码 256-265出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2011.08.045
关键词
Lung cancer; Gene therapy; Poly(amino ester); Spermine; Aerosol delivery
资金
- MKE/KEIT [10035333]
- National Research Foundation, Ministry of Education, Science and Technology (MEST) in Korea [NRF-2011-0000380]
- Brain Korea 21 Program
- Research Institute for Veterinary Science, Seoul National University
- Korea Evaluation Institute of Industrial Technology (KEIT) [10035333] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Polyethylenimine (PEI) has been commonly used as a cationic polymeric gene carrier due to high transfection efficiency, however, its cytotoxicity has hindered the practical application. In this study, we report the development of poly(amino ester) (PAE) based on glycerol propoxylate triacrylate (GPT) and spermine (SPE) as an alternative gene carrier for lung cancer therapy. GPT-SPE copolymer was prepared by Michael addition reaction between GPT and SPE, and the efficacy was evaluated using shAkt1 as a model therapeutic gene. The molecular weight and composition were characterized using gel permeability chromatography (GPC) and H-1-nuclear magnetic resonance (H-1-NMR), respectively. The GPT-SPE could effectively condense DNA with about 163 nm size and protect the DNA from nucleases. GPT-SPE/DNA complexes showed excellent transfection with low toxicity both in vitro and in vivo. Furthermore, aerosol delivery of GPT-SPE/Akt1 shRNA complexes significantly suppressed lung tumorigenesis in K-ras(LA1) lung cancer model mice. These results suggest that GPT-SPE can be used in shRNA-based lung cancer gene therapy. (c) 2011 Elsevier B.V. All rights reserved.
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