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Antitumoral efficacy of DNA nanoparticles in murine models of lung cancer and pulmonary metastasis

Cancer Gene Therapy volume 17, pages 20–27 (2010)Cite this article

Abstract

Polyethylenimine (PEI)–DNA complexes are nanoparticles that are able to efficiently transfer plasmids to the lungs. Interleukin-12 (IL12) gene transfer using PEI may represent an important strategy for lung cancer treatment. In this study, we evaluated the antitumoral efficacy of the administration of PEI–DNA nanoparticles carrying IL12 gene (PEI–IL12) for the treatment of lung cancer and pulmonary metastases in animal models. After inoculation of tumor cells, mice were treated intravenously with a single dose of PEI–IL12, PEI nanoparticles carrying the reporter gene β-galactosidase (PEI–LacZ) or vehicle. Transgene expression, survival rates and immune response were analyzed in both models. Administration of PEI–LacZ and PEI–IL12 nanoparticles controlled tumor growth and prolonged survival times in both animal models. Although PEI–IL12 and PEI–LacZ administration showed similar antitumoral effects in the lung cancer model, the efficacy of PEI–IL12 was significantly superior in the inhibition of the development of pulmonary metastases. Furthermore, the administration of PEI–DNA nanoparticles results in the production of high levels of proinflammatory cytokines. Our results showed that PEI–DNA nanoparticles are an efficient vector for mediating gene transfer to the lungs, are a potent inducer of the innate immune response and represents an interesting strategy for the treatment of bronchogenic carcinoma and metastatic lung carcinoma.

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Acknowledgements

The authors thank Cristina Olague and Africa Vales for their technical support. We thank CIFA staff for animal care. Supported in part by grants of the UTE project CIMA, Instituto Salud Carlos III C03/02, SAF 2006-03623 (Ministerio Educación y Ciencia) to G. G-A, J.C. P. B. and by Department of Education and Culture of the Government of Navarra (IIQ4273). M.R.G. is a recipient of a ‘Fundación Echebano’ fellowship. PB is a recipient of a ‘Juan de la Cierva’ contract.

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Authors and Affiliations

  1. Division of Hepatology and Gene Therapy, Center for Investigation in Applied Medicine (CIMA), University of Navarra, Pamplona, Navarra, Spain

    M Rodrigo-Garzón, P Berraondo, L Ochoa & G González-Aseguinolaza

  2. Department of Respiratory Diseases, University Clinic of Navarra, University of Navarra, Pamplona, Navarra, Spain

    M Rodrigo-Garzón & J J Zulueta

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  1. M Rodrigo-Garzón
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  2. P Berraondo
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  3. L Ochoa
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Correspondence to G González-Aseguinolaza.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website (http://www.nature.com/cgt)

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Rodrigo-Garzón, M., Berraondo, P., Ochoa, L. et al. Antitumoral efficacy of DNA nanoparticles in murine models of lung cancer and pulmonary metastasis. Cancer Gene Ther 17, 20–27 (2010). https://doi.org/10.1038/cgt.2009.45

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