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Título: | Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment |
Autor: | Lores, Saínza; Gamez-Chiachio, Manuel CSIC ORCID; Cascallar, María; Ramos-Nebot, Carmen; Hurtado, Pablo; López López, Rafael; Piñeiro, Roberto; Moreno-Bueno, Gema CSIC ORCID; Fuente, María de la | Fecha de publicación: | 2023 | Editor: | Royal Society of Chemistry (UK) | Citación: | Biomaterials Science 11: 4210- 4225 (2023) | Resumen: | Gene therapy has long been proposed for cancer treatment. However, the use of therapeutic nucleic acids presents several limitations such as enzymatic degradation, rapid clearance, and poor cellular uptake and efficiency. In this work we propose the use of putrescine, a precursor for higher polyamine biosynthesis for the preparation of cationic nanosystems for cancer gene therapy. We have formulated and characterized putrescine-sphingomyelin nanosystems (PSN) and studied their endocytic pathway and intracellular trafficking in cancer cells. After loading a plasmid DNA (pDNA) encoding the apoptotic Fas Ligand (FasL), we proved their therapeutic activity by measuring the cell death rate after treatment of MDA-MB-231 cells. We have also used xenografted zebrafish embryos as a first in vivo approach to demonstrate the efficacy of the proposed PSN-pDNA formulation in a more complex model. Finally, intratumoral and intraperitoneal administration to mice-bearing MDA-MB-231 xenografts resulted in a significant decrease in tumour cell growth, highlighting the potential of the developed gene therapy nanoformulation for the treatment of triple negative breast cancer. | Versión del editor: | http://dx.doi.org/10.1039/d2bm01456d | URI: | http://hdl.handle.net/10261/340104 | DOI: | 10.1039/d2bm01456d | ISSN: | 2047-4849 | E-ISSN: | 2047-4830 |
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Effectiveness_of_a_novel_gene nanotherapy_Lores_PV_Art2023.pdf | 4,66 MB | Adobe PDF | Visualizar/Abrir |
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