Antitumoral efficacy of DNA nanoparticles in murine models of lung cancer and pulmonary metastasis
Rodrigo-Garzón M, Berraondo P, Ochoa L, Zulueta JJ, González-Aseguinolaza G.
Division of Hepatology and Gene Therapy, Center for Investigation in Applied Medicine, University of Navarra, Pamplona, Navarra, Spain.
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 beta-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.
CITA DEL ARTÍCULO Cancer Gene Ther. 2010 Jan;17(1):20-7