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NT-polyplex: a new tool for therapeutic gene delivery to neuroblastoma tumors

Cancer Gene Therapy volume 16, pages 573–584 (2009)Cite this article

Abstract

Neurotensin (NT)-polyplex is a nonviral system for the targeted gene delivery to cells that express and internalize the high-affinity NT receptor (NTSR1). In hemiparkinsonian rats, we previously demonstrated the morphological and functional recovery from dopaminergic neurodegeneration using the NT-polyplex as a vehicle to transfect a neurotrophic gene. The main objective of this work was to demonstrate the feasibility of NT-polyplex to transfect reporter or therapeutic genes into neuroblastoma tumors through the blood stream or by intratumoral injection. N1E-115 cells known to express NTSR1 were allografted into athymic mice to generate the neuroblastoma tumor model. Both routes of administration allowed the NT-polyplex to reach and transfect tumoral cells. A low transgene expression was also detected in intestinal tract cells only after the injection into the blood stream. The transfection of the thymidine kinase (HSVTK) suicide gene followed by ganciclovir (GCV) treatment decreased the size and weight of neuroblastoma tumors by 30–50% and increased apoptosis compared to controls. This study shows the potential of the NT-polyplex as specific gene-transfer system for NTSR1 cancer cells.

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Acknowledgements

Hector A Rubio-Zapata was recipient of scholarships from CONACYT. Dr Martha L Arango-Rodriguez receives a postdoctoral fellowship from cinvestav-I.P.N. This work was supported by El Instituto de Ciencia y Tecnología del Distrito Federal (grant ICYTDF-DMF) and by SEP-CONACYT-ECOS (Grant M07-S01). Thanks to Dr Ellis Glazier for the editing of the English language text.

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Authors and Affiliations

  1. Department of Physiology, Biophysics and Neuroscience, CINVESTAV, Mexico DF, Mexico

    H A Rubio-Zapata, M L Arango-Rodriguez & D Martinez-Fong

  2. School of Medicine, UADY, Merida, Yucatan, Mexico

    H A Rubio-Zapata

  3. Department of Neuropathology, INNN, Mexico DF, Mexico

    J D Rembao-Bojorquez

  4. Molecular and Steroid hormones, Neurotensin and Tumor Progression INSERM UPMC Cdr Saint-Antoine Eq 7, Paris, France

    S Dupouy & P Forgez

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  1. H A Rubio-Zapata
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Correspondence to D Martinez-Fong.

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Rubio-Zapata, H., Rembao-Bojorquez, J., Arango-Rodriguez, M. et al. NT-polyplex: a new tool for therapeutic gene delivery to neuroblastoma tumors. Cancer Gene Ther 16, 573–584 (2009). https://doi.org/10.1038/cgt.2009.1

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