Suicide HSVtk Gene Delivery by Neurotensin-Polyplex Nanoparticles via the Bloodstream and GCV Treatment Specifically Inhibit the Growth of Human MDA-MB-231 Triple Negative Breast Cancer Tumors Xenografted in Athymic Mice

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dc.contributor.authorCastillo-Rodríguez, Rosa
dc.contributor.authorArango-Rodríguez, Martha
dc.contributor.authorEscobedo, Lourdes
dc.contributor.authorHernandez-Baltazar, Daniel
dc.contributor.authorGompel, Anne
dc.contributor.authorForgez, Patricia
dc.contributor.authorMartínez-Fong, Daniel
dc.date.accessioned2017-03-13T19:43:09Z
dc.date.available2017-03-13T19:43:09Z
dc.date.issued2014
dc.descriptionCentro de Medicina Regenerativa
dc.description.abstractThe human breast adenocarcinoma cell line MDA-MB-231 has the triple-negative breast cancer (TNBC) phenotype, which is an aggressive subtype with no specific treatment. MDA-MB-231 cells express neurotensin receptor type 1 (NTSR1), which makes these cells an attractive target of therapeutic genes that are delivered by the neurotensin (NTS)-polyplex nanocarrier via the bloodstream. We addressed the relevance of this strategy for TNBC treatment using NTS-polyplex nanoparticles harboring the herpes simplex virus thymidine kinase (HSVtk) suicide gene and its complementary prodrug ganciclovir (GCV). The reporter gene encoding green fluorescent protein (GFP) was used as a control. NTS-polyplex successfully transfected both genes in cultured MDA-MB-231 cells. The transfection was demonstrated pharmacologically to be dependent on activation of NTSR1. The expression of HSVtk gene decreased cell viability by 49% (P<0.0001) and induced apoptosis in cultured MDA-MB-231 cells after complementary GCV treatment. In the MDA-MB-231 xenograft model, NTS-polyplex nanoparticles carrying either the HSVtk gene or GFP gene were injected into the tumors or via the bloodstream. Both routes of administration allowed the NTS-polyplex nanoparticles to reach and transfect tumorous cells. HSVtk expression and GCV led to apoptosis, as shown by the presence of cleaved caspase-3 and Apostain immunoreactivity, and significantly inhibited the tumor growth (55–60%) (P<0.001). At the end of the experiment, the weight of tumors transfected with the HSVtk gene was 55% less than that of control tumors (P<0.05). The intravenous transfection did not induce apoptosis in peripheral organs. Our results offer a promising gene therapy for TNBC using the NTS-polyplex nanocarrier.
dc.format.extent12
dc.identifier.citationPLoS One. 2014 May 13;9(5):e97151
dc.identifier.urihttp://hdl.handle.net/11447/1019
dc.identifier.urihttp://dx.doi.org/ 10.1371/journal.pone.0097151
dc.language.isoen_US
dc.publisherPublic Library of Science
dc.subjectAnimals
dc.subjectCell Proliferation/drug effects
dc.subjectGenetic Therapy/methods
dc.subjectMice
dc.subjectNanoparticles/metabolism
dc.subjectTriple Negative Breast Neoplasms/physiopathology
dc.titleSuicide HSVtk Gene Delivery by Neurotensin-Polyplex Nanoparticles via the Bloodstream and GCV Treatment Specifically Inhibit the Growth of Human MDA-MB-231 Triple Negative Breast Cancer Tumors Xenografted in Athymic Mice
dc.typeArtículo

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