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Amphiphilic triblock copolymer poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol), enhancement of gene expression and inhibition of lung metastasis by aerosol delivery

Gene Therapy volume 14, pages 476–483 (2007)Cite this article

Abstract

We describe the development of an aerosol system for topical gene delivery to the lungs of C57BL/6 mice. This system is based on the combination of the commercial cationic lipid Lipofectin with a novel amphiphilic triblock copolymer, poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol) (PPDO/PLLA-b-PEG, and abbreviated in the text as polymeric micelles). After optimizing conditions for DNA delivery to the lungs of mice using the combination of polymeric micelles with Lipofectin and LacZ DNA, we used the Lipofectin/polymeric micelle system to deliver the tumor suppressor gene PTEN to the lungs of C57BL/6 mice bearing the B16-F10 melanoma. Lipofectin/PTEN/polymeric micelles significantly improved gene expression of PTEN in the lungs of mice with no evidence of cell toxicity or acute inflammation. Importantly, lung metastasis, as measured by lung weight, was significantly reduced (P<0.001), as were total tumor foci in the lungs (P<0.001) and size of individual tumor nodules in animals treated with Lipofectin/PTEN/polymeric micelles compared with control animals. Survival time was also extended. These results suggest that the Lipofectin/polymeric micelle system is appropriate for enhancing gene delivery in vivo and that it can be applied as a non-invasive gene therapy for lung cancer.

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Acknowledgements

This work was supported by the Korea Research Foundation grant (KRF-2003-041-E20140). We thank Dr Zena K Indik for careful review of the paper and comments.

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Authors and Affiliations

  1. Department of Bionanosystem Engineering, Chonbuk National University, Jeonju, South Korea

    S R Bhattarai

  2. Department of Pediatrics and Research Institute of Clinical Medicine, School of Medicine, Chonbuk National University, Jeonju, South Korea

    S Y Kim, D Y Lee & P H Hwang

  3. Department of Pathology, School of Medicine, Chonbuk National University, Jeonju, South Korea

    K Y Jang

  4. Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju, South Korea

    H K Yi

  5. Department of Anatomy, School of Dentistry, Chonbuk National University, Jeonju, South Korea

    Y H Lee

  6. Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA

    N Bhattarai

  7. Department of Biological Science, School of Science and Technology, Jeonju University, Jeonju, South Korea

    S-Y Nam

  8. Department of Textile Engineering, Chonbuk National University, Jeonju, South Korea

    H Y Kim

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  1. S R Bhattarai
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Correspondence to P H Hwang.

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Supplementary information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Bhattarai, S., Kim, S., Jang, K. et al. Amphiphilic triblock copolymer poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol), enhancement of gene expression and inhibition of lung metastasis by aerosol delivery. Gene Ther 14, 476–483 (2007). https://doi.org/10.1038/sj.gt.3302876

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