Antitumoral efficacy of DNA nanoparticles in murine models of lung cancer and pulmonary metastasis.
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.
Rodrigo-Garzón
M
M
Division of Hepatology and Gene Therapy, Center for Investigation in Applied Medicine, University of Navarra, Pamplona, Navarra, Spain.
Berraondo
P
P
Ochoa
L
L
Zulueta
J J
JJ
González-Aseguinolaza
G
G
D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011094:Polyethyleneimine / Q000008:administration & dosage; D014162:Transfection; D019076:Transgenes
D018664:Interleukin-12; D011094:Polyethyleneimine; D004247:DNA